Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Secretion

  • acid secretion
  • acth secretion
  • airway secretion
  • albumin secretion
  • aldosterone secretion
  • amylase secretion
  • anion secretion
  • antibody secretion
  • antidiuretic hormone secretion
  • apob secretion
  • bicarbonate secretion
  • bile secretion
  • biliary secretion
  • catecholamine secretion
  • cell secretion
  • chemokine secretion
  • chloride secretion
  • constitutive secretion
  • corticosterone secretion
  • cortisol secretion
  • cytokine secretion
  • decapitation secretion
  • dense granule secretion
  • dopamine secretion
  • dry secretion
  • enhanced secretion
  • enzyme secretion
  • excessive secretion
  • exocrine pancreatic secretion
  • exocrine secretion
  • factor secretion
  • first-phase insulin secretion
  • fluid secretion
  • gastric acid secretion
  • gastric secretion
  • gh secretion
  • ghrelin secretion
  • gland secretion
  • glandular secretion
  • glucagon secretion
  • glucocorticoid secretion
  • glucose-induced insulin secretion
  • glucose-stimulated insulin secretion
  • gonadotropin secretion
  • granule secretion
  • growth factor secretion
  • growth hormone secretion
  • hormone secretion
  • igg secretion
  • iii secretion
  • il-10 secretion
  • il-4 secretion
  • il-5 secretion
  • il-6 secretion
  • il-8 secretion
  • inappropriate antidiuretic hormone secretion
  • inappropriate secretion
  • increased insulin secretion
  • increased secretion
  • induced secretion
  • insulin secretion
  • intestinal secretion
  • iv secretion
  • leptin secretion
  • lh secretion
  • lipid secretion
  • mcp-1 secretion
  • melatonin secretion
  • mmp-2 secretion
  • mucosal secretion
  • mucous secretion
  • mucus secretion
  • nasal secretion
  • nectar secretion
  • oral secretion
  • oxytocin secretion
  • pancreatic enzyme secretion
  • pancreatic insulin secretion
  • pancreatic secretion
  • peptide secretion
  • prl secretion
  • pro-inflammatory cytokine secretion
  • progesterone secretion
  • prolactin secretion
  • prostatic secretion
  • protein secretion
  • psa secretion
  • salivary secretion
  • sebum secretion
  • skin secretion
  • tear secretion
  • testosterone secretion
  • total insulin secretion
  • tract secretion
  • tubular secretion
  • type iii secretion
  • type iv secretion
  • vaginal secretion
  • vasopressin secretion
  • vegf secretion

  • Terms modified by Secretion

  • secretion level
  • secretion machinery
  • secretion mechanism
  • secretion pathway
  • secretion pattern
  • secretion process
  • secretion profile
  • secretion rate
  • secretion signal
  • secretion substrate
  • secretion system

  • Selected Abstracts


    Ervin Tth
    Background:, The conventional endoscopic Congo red test (CRT) permits visualization of acid-producing mucosa. However, the CRT has not been disseminated into clinical endoscopy, which is partly due to the substantial prolongation of the gastroscopic examination. Methods:, Five healthy volunteers and 551 patients were included in a study designed to develop a more rapid approach based on the CRT. In this modified endoscopic Congo red test (MCRT), 0.2 g/kg of pentagastrin was given intravenously to stimulate gastric acid production. The technical feasibility, tolerability, reproducibility, and inter- and intra-observer reliability of the MCRT were evaluated. Results:, The MCRT was as effective as the CRT (i.e. 6 g/kg of pentagastrin was administered intramuscularly) in visualizing the extent of acid-producing gastric mucosa. Moreover, the MCRT significantly reduced the duration of examination by 63% (almost 8 min), compared to the CRT. Conclusions:, This MCRT is a simple, inexpensive, well-tolerated and reproducible method with low inter- and intra-observer variability and is well suited for endoscopy units with high workloads. [source]

    Effects of contaminated sediment on the epidermis of mummichog, Fundulus heteroclitus

    Laurent C. Mzin
    Abstract Secretion of mucus by epidermal goblet cells protects fish against many biological, physical, and chemical insults encountered in the environment. This study monitored changes in hemoglobin concentration in epidermal mucus and in the density, diameter, and mucus quality of epidermal goblet cells in the mummichog, Fundulus heteroclitus, following exposure to creosote-contaminated sediment from the Elizabeth River, Virginia, USA. Fish were exposed for 13 d in flow-through aquaria to either uncontaminated (US) or contaminated (CS) sediments and were sampled periodically. The condition index was lower and the mortality rate and the occurrence of epidermal lesions were higher in CS-exposed fish than in US-exposed fish. Hemoglobin contents in epidermal mucus from the former group were significantly higher than from the latter. Significant reductions in both size and density of goblet cells in CS-exposed fish suggested a mucus secretion rate exceeding its production rate. Significant changes in mucin types between treatments did not occur until day 13 and are not believed to be directly related to the creosote present in the contaminated sediment. These results all indicate that exposure to creosote-contaminated sediment had a profound and deleterious effect on fish health. [source]

    Exocrine pancreatic dysfunction in sepsis

    B. Tribl
    Abstract Background Sepsis in critical illness is associated with the progressive failure of multiple organs. This study aims to establish a correlation between the severity of sepsis and exocrine pancreatic dysfunction. Materials and methods In a prospective cohort study pancreatic exocrine function was tested by means of a secretin-cholecystokinin test in 21 critically ill, mechanically ventilated patients with sepsis according to criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (ACCP/SCCM): 11 patients with shock and 10 patients without shock. Data were compared with seven healthy controls. Results The volume of duodenal fluid was not statistically different in the three groups. Sepsis patients without shock had significantly reduced content of amylase and chymotrypsin in duodenal juice compared with healthy controls (P < 001). Secretion of amylase, chymotrypsin, trypsin (P < 001 each) and bicarbonate in duodenal fluid (P < 005) was impaired in the septic shock patients when compared with the healthy controls. The content of trypsin was different between sepsis patients and septic shock patients (P < 005). Spearman correlation analysis was significant between the amylase secretion and the APACHE III and SOFA scores (P < 001). The SOFA score was also related to secretion of trypsin (P < 005). In patients on pressor therapy, use of norepinephrine was associated with a significant decrease in bicarbonate secretion (P < 005). Conclusions Sepsis is associated with secretory pancreatic dysfunction that is worse in septic shock than in sepsis without shock. Impaired exocrine function was significantly correlated to the APACHE III and SOFA scores. [source]

    ,-tocopherol improves impaired physiology of rat type II pneumocytes isolated from experimentally injured lungs

    B. Mller
    Background Oxidant stress delivered by nitrogen dioxide (NO2) inhalation impairs the function of extracellular surfactant as well as surfactant phospholipid metabolism in type II pneumocytes. Because protection against oxidant stress is important to normal lung function, the lung contains a variety of antioxidants, including vitamin E. Whether administration of this antioxidant during NO2 inhalation attenuates NO2 -induced alterations in phospholipid metabolism in type II pneumocytes has not been studied. Methods We exposed rats to identical NO2 body doses (720 p.p.m. x h) using continuous, intermittent, or repetitive protocols. During exposure periods, the animals received daily intramuscular injections of vitamin E (25 mg kg,1). We isolated type II pneumocytes from NO2 -exposed rats and evaluated them for cell yield and viability, as well as for synthesis and secretion of phosphatidylcholine (PC) as measures of surfactant metabolism. Results The yield of type II pneumocytes was significantly elevated from animals that had been exposed continuously to NO2 whereas in intermittently and repeatedly exposed rats, cell yield was similar to yield from control animals. Viability of the isolated cells was similar in controls and all NO2 exposure protocols. Vitamin E treatment of the NO2 -exposed rats neither changed cell yield nor cell viability. Phospholipid de novo synthesis, as estimated by choline incorporation into PC, was increased most after continuous NO2 inhalation whereas in the other conditions there was only a slight increase. Vitamin E administration further increased phospholipid synthesis; this difference reached statistical significance only in the case of intermittent NO2 exposure. Secretion of phosphatidylcholine from type II cells was only reduced after continuous NO2 inhalation and administration of the antioxidant reduced the impairment. Conclusion Because vitamin E appears to preserve the ability of type II pneumocytes isolated from NO2 -exposed rats to synthesize and secrete surfactant lipid, we conclude that administration of vitamin E may mitigate NO2 -induced lung injury. [source]

    AgC10, a mucin from Trypanosoma cruzi, destabilizes TNF and cyclooxygenase-2 mRNA by inhibiting mitogen-activated protein kinase p38

    Pilar Alcaide
    Abstract Secretion of proinflammatory mediators by activated macrophages plays an important role in the immune response to Trypanosoma cruzi. We have previously reported that AgC10, a glycosylphosphatidylinositol-anchored mucin from T. cruzi, inhibits TNF secretion by activated macrophages (de Diego, J., Punzon, C., Duarte, M. and Fresno, M., Alteration of macrophage function bya Trypanosoma cruzi membrane mucin. J. Immunol. 1997. 159: 4983,4989). In this report we have further investigated the molecular mechanisms underlying this inhibition. AgC10 inhibited TNF, IL-10 and cyclooxygenase-2 (COX-2) synthesis by macrophages activated with LPS or LPS plus IFN-, in a dose-dependent manner. AgC10 did not affect other aspects of macrophage activation induced by LPS, such as inducible nitric oxide synthase (iNOS) expression. AgC10 also had no effect on TNF or COX-2 transcription or the induction of their promoters but inhibited the stability of TNF and COX-2 mRNA, which are regulated post-transcriptionally by the mitogen-activated protein kinase (MAPK) p38 pathway. AgC10 was found to inhibit both the activation and the activity of p38 MAPK, since MAPK activated protein kinase-2 (MAPKAP-K2 or MK-2) phosphorylation was also strongly inhibited. This led to TNF and COX-2 mRNA destabilization. In contrast, AgC10 did not affect p38 activation induced by TNF. Furthermore, AgC10 inhibition must lie upstream in the MAPK activation pathway by LPS, since this mucin also inhibited extracellularly regulated kinase (ERK) and Jun kinase (JNK)activation. [source]

    Constitutive Secretion of Immunoglobulin a and Other Proteins into Lumina of Unstimulated Submandibular Glands in Anaesthetised Rats

    G. B. Proctor
    Salivary fluid secretion is dependent upon reflex stimuli mediated by autonomic nerves. In order to determine if immunoglobulin A (IgA) and salivary proteins are secreted in the absence of nerve stimulation, small volumes (< 2 l) of saliva were consecutively collected from the submandibular duct of anaesthetised rats following rest pauses in order to sample the protein contents of the ductal system. Within the first 5 l of such saliva collected by parasympathetic nerve stimulation, IgA and other salivary proteins reached peak concentrations that were over 20-fold greater than levels in parasympathetically stimulated saliva subsequently collected during a 5 min period of stimulation. Confocal microscopy of TRITC-labelled IgA added to live, acutely isolated submandibular acini indicated that it did not enter the lumina by paracellular leakage. IgG is thought to enter saliva by paracellular leakage but did not accumulate in luminal saliva in the present study. Electrophoresis suggested that the major proteins secreted in the absence of stimulation were the same as those present in subsequently stimulated saliva. It can be concluded that IgA and other major submandibular proteins are secreted into glandular lumina in the absence of nerve stimulation. The functional significance of such unstimulated protein secretion is at present unclear. [source]

    Secretion of proteases in serglycin transfected Madin,Darby canine kidney cells

    FEBS JOURNAL, Issue 3 2006
    Lillian Zernichow
    Madin,Darby canine kidney (MDCK) cells, which do not normally express the proteoglycan (PG) serglycin, were stably transfected with cDNA for human serglycin fused to a polyhistidine tag (His-tag). Clones with different levels of serglycin mRNA expression were generated. One clone with lower and one with higher serglycin mRNA expression were selected for this study. 35S-labelled serglycin in cell fractions and conditioned media was isolated using HisTrap affinity chromatography. Serglycin could also be detected in conditioned media using western blotting. To investigate the possible importance of serglycin linked to protease secretion, enzyme activities using chromogenic substrates and zymography were measured in cell fractions and serum-free conditioned media of the different clones. Cells were cultured in both the absence and presence of phorbol 12-myristate 13-acetate (PMA). In general, enzyme secretion was strongly enhanced by treatment with PMA. Our analyses revealed that the clone with the highest serglycin mRNA expression, level of HisTrap isolated 35S-labelled serglycin, and amount of serglycin core protein as detected by western blotting, also showed the highest secretion of proteases. Transfection of serglycin into MDCK cells clearly leads to changes in secretion levels of secreted endogenous proteases, and could provide further insight into the biosynthesis and secretion of serglycin and potential partner molecules. [source]

    Secretion of the Escherichia coli K-12 SheA hemolysin is independent of its cytolytic activity

    Francisco J del Castillo
    Abstract The Escherichia coli K-12 sheA gene encodes a pore-forming hemolysin that is secreted to the medium by a hitherto unidentified mechanism. To study SheA secretion, we constructed fusions between SheA and the mature form of the periplasmic enzyme ,-lactamase, and performed site-directed mutagenesis on these constructs. The SheA-Bla and Bla-SheA hybrid proteins displayed hemolytic activity and were efficiently exported to the extracellular medium. Our results with mutant hybrid proteins show that secretion of SheA is independent of its cytolytic activity, that secretion is paralleled by a transient leakage of periplasmic contents to the extracellular medium, and that deletion of the 11 C-terminal residues of SheA has no effect on its secretion and cytolytic activity. [source]

    Increase of calnexin gene dosage boosts the secretion of heterologous proteins by Hansenula polymorpha

    FEMS YEAST RESEARCH, Issue 7 2007
    Jens Klabunde
    Abstract The type I membrane protein calnexin is a conserved key component of the quality control mechanism in the endoplasmic reticulum. It functions as a molecular chaperone that monitors the folding state of nascent polypeptides entering the endoplasmic reticulum. Calnexin also behaves as a lectin, as its chaperoning activity involves binding of oligosaccharide moieties present on newly imported glycoproteins. We isolated the calnexin gene (HpCNE1) from the methylotrophic yeast Hansenula polymorpha, and used HpCNE1 expression plasmids for supertransformation of H. polymorpha strains secreting target proteins of biotechnological interest. The elevated dosage of HpCNE1 enhanced secretion of the four proteins tested: three glycoproteins and one unglycosylated product. Secretion of bacterial alginate epimerase AlgE1 was increased threefold on average, and secretion of both human interferon-, and fungal consensus phytase twofold. With phytase and AlgE1 this improvement was all the more remarkable, as the secretion level was already high in the original strains (g L,1 range). The same approach improved secretion of human serum albumin, which lacks N-linked glycans, about twofold. Glycosylation of the pro-MF,1 leader may account for the effect of calnexin in this case. Our results argue that cooverexpression of calnexin can serve as a generally applicable tool for enhancing the secretion of all types of heterologous protein by H. polymorpha. [source]

    Secretion of matrix metalloproteinase-9 by the proinflammatory cytokine, IL-1,: a role for the dual signalling pathways, Akt and Erk

    GENES TO CELLS, Issue 6 2003
    A. R. M. Ruhul Amin
    Background: Matrix metalloproteinases including MMP-9 mediate matrix destruction during chronic inflammatory diseases such as arthritis and atherosclerosis. MMP-9 up-regulation by inflammatory cytokines involve interactions between several transcription factors including activator protein-1 and NF,B. The upstream regulatory pathways are less well understood. Results: To search for the mechanism of tissue destruction in the process of inflammatory disorders, we investigated the signalling pathway critical for the activation of MMP-9 expression and secretion by IL-1,. Treatment of Balb 3T3 cells with IL-1, activated MMP-9 transcription and subsequent secretion in a time- and dose-dependent manner. Concomitantly, IL-1, treatment of cells activated phosphorylation of Akt, Erk and p38. Treatment of cells with either LY294002, a PI3K inhibitor, or expression of a dominant negative form of Akt drastically suppressed the IL-1,-dependent secretion of MMP-9. Pretreatment of cells with a MEK1 inhibitor, U0126, also strongly inhibited IL-1,-dependent secretion of MMP-9. In contrast, pre-treatment with a specific p38 kinase inhibitor, SB203580, had no effect on IL-1,-dependent secretion of MMP-9. In addition, cells expressing constitutively active form of Akt or MEK1 showed no clear activation of MMP-9 secretion, whereas these cells responded well to IL-1, treatment. However, co-transfection of cells with both active Akt and MEK1 was sufficient to induce MMP-9 secretion without stimulation with IL-1,. Conclusion: Taken together, our results suggest that IL-1, stimulation of cells activates MMP-9 secretion by the activation of the dual signalling pathways, the PI3K-Akt and MEK1-Erk and constitutive activation of these pathways were sufficient to induce MMP-9 secretion. [source]

    Effect of Helicobacter pylori Infection on Gastric Acid Secretion and Meal-Stimulated Serum Gastrin in Children

    HELICOBACTER, Issue 2 2004
    Seiichi Kato
    ABSTRACT Background., Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods., Thirty-six children aged 10,17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2,3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication. Results.,H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori- positive patients with duodenal ulcer than in gastritis-only patients or controls [mean standard error (SE): 6.56 1.4, 3.11 0.4 and 2.65 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori- positive boys than girls (5.0 0.8 vs. 2.51 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre- and post- H. pylori eradication was similar (5.47 0.8 vs. 4.67 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions.,H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection. [source]

    Secretion of interferon-, by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18

    IMMUNOLOGY, Issue 3 2009
    Laila Darwich
    Summary The interferon (IFN)-, component of the immune response plays an essential role in combating infectious and non-infectious diseases. Induction of IFN-, secretion by human T and natural killer (NK) cells through synergistic costimulation with interleukin (IL)-12 and IL-18 in the adaptive immune responses against pathogens is well established, but induction of similar activity in macrophages is still controversial, with doubts largely focusing on contamination of macrophages with NK or T cells in the relevant experiments. The possible contribution of macrophages to the IFN response is, however, an important factor relevant to the pathogenesis of many diseases. To resolve this issue, we analysed the production of IFN-, at the single-cell level by immunohistochemistry and by enzyme-linked immunosorbent spot (ELISPOT) analysis and unequivocally demonstrated that human macrophages derived from monocytes in vitro through stimulation with a combination of IL-12 and IL-18 or with macrophage colony-stimulating factor (M-CSF) were able to produce IFN-, when further stimulated with a combination of IL-12 and IL-18. In addition, naturally activated alveolar macrophages immediately secreted IFN-, upon treatment with IL-12 and IL-18. Therefore, human macrophages in addition to lymphoid cells contribute to the IFN-, response, providing another link between the innate and acquired immune responses. [source]

    Examination of the signal transduction pathways leading to upregulation of tissue type plasminogen activator by Porphyromonas endodontalis in human pulp cells

    F.-M. Huang
    Abstract Aim, To investigate the tissue type plasminogen activator (t-PA) activity in human pulp cells stimulated with Porphyromonas endodontalis (P. endodontalis) in the absence or presence of p38 inhibitor SB203580, mitogen-activated protein kinase kinase (MEK) inhibitor U0126 and phosphatidylinositaol 3-kinase (PI3K) inhibitor LY294002. Methodology, The supernatants of P. endodontalis were used to evaluate t-PA activity in human pulp cells using casein zymography and enzyme-linked immunosorbent assay (ELISA). Furthermore, to search for possible signal transduction pathways, SB203580, U0126 and LY294002 were added to test how they modulated the t-PA activity. Results, The main casein secreted by human pulp cells migrated at 70 kDa and represented t-PA. Secretion of t-PA was found to be stimulated with P. endodontalis during 2-day cultured period (P < 0.05). From the results of casein zymography and ELISA, SB203580 and U0126 significantly reduced the P. endodontalis stimulated t-PA production respectively (P < 0.05). However, LY294002 lacked the ability to change the P. endodontalis stimulated t-PA production (P > 0.05). Conclusions,Porphyromonas endodontalis enhances t-PA production in human pulp cells, and the signal transduction pathways p38 and MEK are involved in the inhibition of t-PA. [source]

    Sequential secretion of collagenolytic, elastolytic, and keratinolytic proteases in peptide-limited cultures of two Bacillus cereus strains isolated from wool

    A.C. Ad, gzel
    Abstract Aims:, To characterize the secretion of proteolytic activities against keratin, collagen and elastin in liquid cultures of Bacillus cereus IZ-06b and IZ-06r isolated from wool. Methods and Results:, Growth of B. cereus IZ-06b and IZ-06r were characterized in batch culture. Both strains needed an organic nitrogen source, were able to grow on wool or peptone as sole carbon and nitrogen sources, and metabolized glucose, maltose and other simple sugars. Proteolytic activities were investigated in batch cultures grown in peptide-restricted, carbon-sufficient medium. Secretion of proteases was induced by peptide limitation while different proteolytic activities appeared sequentially in the growth medium. When the most available components of the peptone were depleted, collagenolytic and elastolytic proteases were produced. These were later replaced by the production of keratinolytic protease. Conclusions:,B. cereus can adjust its proteolytic affinity profile in response to the supply of organic nitrogen and sequentially secrete proteases with activities targeted against increasingly inaccessible proteinous substrates as the nutritional availability in the environment deteriorates. Significance and Impact of the Study:, Peptide-limited, carbon-sufficient growth media containing no proteinous substrates are well suited for protease production in B. cereus while growth conditions can be adjusted to optimize the proteolytic affinity profiles. [source]

    Secretion of cortisol and aldosterone as a vulnerable target for adrenal endocrine disruption , screening of 30 selected chemicals in the human H295R cell model

    Erik Ullers
    Abstract The adrenal gland is a vulnerable target for toxic insult. Disruption of adrenal steroidogenesis and hormone secretion may cause serious effects on human health. A human in vitro model is needed to predict effects, and elucidate mechanisms of endocrine disruption and adrenal toxicity. The human adrenocortical cell line H295R has been used to screen for effects on sex hormones. Here, we have analyzed the effect of 30 potential endocrine disrupting chemicals on the secretion of cortisol and aldosterone from the H295R cells, using specific ELISA assays. The effect of chemicals was analyzed for basal and forskolin- or angiotensin II-stimulated hormone secretion. The chemicals were tested at the highest concentration where they displayed no evident unspecific cytotoxicity. Quantitative and qualitative differences in effects on hormone secretion were demonstrated for the various chemicals. A subset of the chemicals displayed different effects on cortisol and aldosterone secretion, and in some cases the effects were different between basal and stimulated hormone secretion. Aminoglutethimide, prochloraz, ketoconazole, 6-hydroxyflavone, imazalil and etomidate had the most marked inhibitory effects on cortisol (with or without forskolin) and ketoconazole, 6-hydroxyflavone, imazalil and etomidate had the most marked effects on aldosterone (with or without angiotensin II). The results are discussed in terms of known effects, structural similarity and possible mechanisms. We have shown that adrenal steroidogenesis is a vulnerable target for toxic insult and that the H295R assay is a useful in vitro model for screening purposes. Copyright 2008 John Wiley & Sons, Ltd. [source]

    Secretion of SDF-1, by bone marrow-derived stromal cells enhances skin wound healing of C57BL/6 mice exposed to ionizing radiation

    Yannick Landry
    Abstract Patients treated for cancer therapy using ionizing radiation (IR) have delayed tissue repair and regeneration. The mechanisms mediating these defects remain largely unknown at present, thus limiting the development of therapeutic approaches. Using a wound healing model, we here investigate the mechanisms by which IR exposure limits skin regeneration. Our data show that induction of the stromal cell-derived growth factor 1, (SDF-1,) is severely impaired in the wounded skin of irradiated, compared to non-irradiated, mice. Hence, we evaluated the potential of bone marrow-derived multipotent stromal cells (MSCs), which secrete high levels of SDF-1,, to improve skin regeneration in irradiated mice. Injection of MSCs into the wound margin led to remarkable enhancement of skin healing in mice exposed to IR. Injection of irradiated MSCs into the wound periphery of non-irradiated mice delayed wound closure, also suggesting an important role for the stromal microenvironment in skin repair. The beneficial actions of MSCs were mainly paracrine, as the cells did not differentiate into keratinocytes. Specific knockdown of SDF-1, expression led to drastically reduced efficiency of MSCs in improving wound closure, indicating that SDF-1, secretion by MSCs is largely responsible for their beneficial action. We also found that one mechanism by which SDF-1, enhances wound closure likely involves increased skin vascularization. Our findings collectively indicate that SDF-1, is an important deregulated cytokine in irradiated wounded skin, and that the decline in tissue regeneration potential following IR can be reversed, given adequate microenvironmental support [source]

    Discovery of the Porosome: revealing the molecular mechanism of secretion and membrane fusion in cells

    B. P. Jena
    Abstract Secretion and membrane fusion are fundamental cellular processes involved in the physiology of health and disease. Studies within the past decade reveal the molecular mechanism of secretion and membrane fusion in cells. Studies reveal that membrane-bound secretory vesicles dock and fuse at porosomes, which are specialized plasma membrane structures. Swelling of secretory vesicles result in a build-up of intravesicular pressure, which allows expulsion of vesicular contents. The discovery of the porosome, its isolation, its structure and dynamics at nm resolution and in real time, its biochemical composition and functional reconstitution, are discussed. The molecular mechanism of secretory vesicle fusion at the base of porosomes, and vesicle swelling, have been resolved. With these findings a new understanding of cell secretion has emerged and confirmed by a number of laboratories. [source]

    Secretion of RANTES (CCL5) and interleukin-10 from mesenteric adipose tissue and from creeping fat in Crohn's disease: Regulation by steroid treatment

    Andreas Schffler
    Abstract Background:, Creeping fat represents a characteristic feature of Crohn's disease (CD) and adipose tissue is currently being recognized as a complex compartment secreting highly active molecules. Pro- or anti-inflammatory adipose tissue-derived secretory products (adipocytokines) might play a role in the pathogenesis of CD. Methods:, Adipose tissue specimens were obtained from creeping fat contiguous to the involved intestine of 10 patients with CD. Mesenteric adipose tissue specimens resected in 13 patients with colon cancer (CC) and in seven patients with diverticulitis (DIV) served as controls. Three fat tissue specimens per well and n = 6,8 wells per patient were incubated ex vivo for 24 h. The release of regulated on activation, T-cell expressed and secreted (RANTES) and interleukin (IL)-10 into the supernatant was measured by ELISA. Results:, Both RANTES and IL-10 secretion could be demonstrated from total adipose tissue explants. The RANTES secretion is increased from creeping fat in CD (3691 597 pg/g fat per 24 h) when compared to mesenteric adipose tissue from patients with CC (1690 191 pg/g fat per 24 h; P < 0.0001) or DIV (1672 336 pg/g fat per 24 h; P < 0.0001). In contrast, IL-10 secretion is downregulated significantly only in patients with DIV (1418 180 pg/g fat per 24 h; P = 0.016) when compared to CC patients (2368 259 pg/g fat per 24 h). Crohn's disease patients receiving steroids had a higher secretion rate of RANTES and IL-10. Conclusions:, Both RANTES and IL-10 secretion can be detected from mesenteric adipose tissue and from creeping fat. The elevated RANTES and IL-10 secretion from creeping fat in CD is not due to a CD-specific effect but caused by steroid treatment. [source]

    Activity of Hypothalamic Dopaminergic Neurones During the Day of Oestrus: Involvement in Prolactin Secretion

    C. M. Leite
    A secretory surge of prolactin occurs on the afternoon of oestrus in cycling rats. Pituitary prolactin is inhibited by dopamine. We evaluated the activity of the neuroendocrine dopaminergic neurones during oestrus and dioestrus, as determined by dopaminergic activity in the median eminence and neurointermediate lobe of the pituitary, as well as Fos-related antigen expression in tyrosine hydroxylase (TH)-immunoreactive (ir) neurones of the arcuate nucleus (ARC) and periventricular nucleus (Pe). During oestrus, the 4-dihydroxyphenylacetic acid/dopamine ratio in the median eminence decreased at 16.00 h, coinciding with the increase in plasma prolactin levels. Similarly, the expression of Fos-related antigen in TH-ir neurones of Pe and rostral-, dorsomedial- and caudal-ARC also decreased at 16.00 h. On dioestrus, 4-dihydroxyphenylacetic acid/dopamine ratio in the median eminence and Fos-related antigen expression in TH-ir neurones of Pe and rostral-ARC decreased at 18.00 h, whereas prolactin levels were unaltered. No variation in dopaminergic activity was found in the neurointermediate lobe of the pituitary on either oestrus or dioestrus. The number of TH-ir neurones in the ARC and parameters of dopaminergic activity were found to be generally lower on oestrus compared to dioestrus. The transitory decrease in the activity of neuroendocrine dopaminergic neurones temporally associated with the prolactin surge on the afternoon of oestrus suggests a role for dopamine in the generation of the oestrous prolactin surge. [source]

    The Ghrelin/Obestatin Balance in the Physiological and Pathological Control of Growth Hormone Secretion, Body Composition and Food Intake

    R. Hassouna
    Ghrelin and obestatin are two gastrointestinal peptides obtained by post-translational processing of a common precursor, preproghrelin. Ghrelin is an orexigenic and adipogenic peptide and a potent growth hormone secretagogue (GHS) modified by the enzyme ghrelin- O -acyl-transferase to bind and activate its receptor, the GHS-R. The ghrelin/GHS-R pathway is complex and the effects of ghrelin on GH secretion, adiposity and food intake appear to be relayed by distinct mechanisms involving different transduction signals and constitutive activity for the GH-R, different cofactors as modulators of endogenous ghrelin signalling and/or alternative ghrelin receptors. The discovery of obestatin in 2005 brought an additional level of complexity to this fascinating system. Obestatin was initially identified as an anorexigenic peptide and as the cognate ligand for GPR39, but its effect on food intake and its ability to activate GPR39 are still controversial. Although several teams failed to reproduce the anorexigenic actions of obestatin, this peptide has been shown to antagonise GH secretion and food intake induced by ghrelin and could be an interesting pharmacological tool to counteract the actions of ghrelin. Ghrelin and obestatin immunoreactivities are recovered in the blood with an ultradian pulsatility and their concentrations in plasma vary with the nutritional status of the body. It is still a matter of debate whether both hormones are regulated by independent mechanisms and whether obestatin is a physiologically relevant peptide. Nevertheless, a significant number of studies show that the ghrelin/obestatin ratio is modified in anorexia nervosa and obesity. This suggests that the ghrelin/obestatin balance could be essential to adapt the body's response to nutritional challenges. Although measuring ghrelin and obestatin in plasma is challenging because many forms of the peptides circulate, more sensitive and selective assays to detect the different preproghrelin-derived peptides are being developed and may be the key to obtaining a better understanding of their roles in different physiological and pathological conditions. [source]

    Stress Response of Prolactin-Releasing Peptide Knockout Mice as to Glucocorticoid Secretion

    A. Mochiduki
    Prolactin-releasing peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP-knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP-KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP-KO mice. As we reported previously, PrRP stimulates corticotrophin-releasing factor and regulates the hypothalamic-pituitary-adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP-KO mice, and found that PrRP-KO mice showed higher concentrations of blood glucose and corticosterone compared to wild-type mice after restraint stress. By contrast, there were no difference in c-Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild-type and PrRP-KO mice. Thus, we conclude that PrRP-KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion. [source]

    Noradrenaline Involvement in the Negative-Feedback Effects of Ovarian Steroids on Luteinising Hormone Secretion

    C. V. V. Helena
    Noradrenaline has been shown to modulate the ovarian-steroid feedback on luteinising-hormone (LH) release. However, despite the high amount of evidence accumulated over many years, the role of noradrenaline in LH regulation is still not clearly understood. The present study aimed to further investigate the involvement of noradrenaline in the negative-feedback effect of oestradiol and progesterone on basal LH secretion. In experiment 1, ovariectomised (OVX) rats received a single injection of oil, oestradiol, or progesterone at 09.00,10.00 h and were decapitated 30 or 60 min later. Levels of noradrenaline and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined in microdissections of the preoptic area (POA) and medial basal hypothalamus-median eminence (MBH-ME) and correlated with LH secretion. Basal LH levels were decreased 30 and 60 min after oestradiol or progesterone injection, and this hormonal response was significantly correlated with a reduction in POA MHPG levels, which reflect noradrenaline release. In addition, noradrenaline levels in the POA were increased, whereas noradrenaline turnover (MHPG/noradrenaline ratio) was decreased 60 min after the injection of both hormones. No effect was found in the MBH-ME. In experiment 2, i.c.v. administration of noradrenaline (60 nmol), performed 15 min before oestradiol or progesterone injection in jugular vein-cannulated OVX rats, completely prevented the ovarian steroid-induced inhibition of LH secretion. The data obtained provide direct evidence that LH secretion in OVX rats is positively regulated by basal noradrenergic activity in the POA, and its reduction appears to play a role in the negative-feedback effect of ovarian steroids on LH secretion in vivo. [source]

    GPR30 Differentially Regulates Short Latency Responses of Luteinising Hormone and Prolactin Secretion to Oestradiol

    D. Lebesgue
    Rapid, nongenomic actions of 17,-oestradiol (E2) on hypothalamic neurones that may be relevant to reproductive function were described decades ago. The orphan G protein-coupled receptor, GPR30, was recently shown to bind oestrogens and to trigger rapid signalling in vitro, and is expressed in several rat and human brain regions, including the hypothalamus. We used two complementary approaches to investigate the role of GPR30 in hypothalamic responses to E2 that are relevant to reproductive physiology. Serial blood sampling after the acute administration of the selective GPR30 agonist G1 was used to assess the role of GPR30 in short latency negative-feedback inhibition of luteinising hormone (LH) secretion and facilitation of prolactin secretion in ovariohysterectomised female rats. In vivo RNA interference (RNAi), mediated by adeno-associated virus-expressing small hairpin RNA (shRNA) infused into the mediobasal hypothalamus, was used to study the effects of GPR30 knockdown on these rapid responses to E2. Longer-term actions of E2 on female sexual behaviour (lordosis) were also examined in female rats subjected to in vivo RNAi. Administration of E2 or G1 triggered a short latency surge of prolactin secretion, and animals subjected to GPR30 RNAi showed significantly less E2 -dependent prolactin release than animals receiving control virus. G1 did not mimic E2 negative-feedback inhibition of LH secretion, and GPR30 RNAi did not interfere with E2 suppression of LH or facilitation of lordosis behaviour. These findings suggest that activation of GPR30 promotes short latency prolactin secretion but does not mediate E2 negative-feedback inhibition of LH secretion or E2 facilitation of female reproductive behaviour. [source]

    Role of the Ventromedial Hypothalamic Orexin-1 Receptors in Regulation of Gastric Acid Secretion in Conscious Rats

    A. Eliassi
    Orexins play an important role on the central nervous system to modulate gastric acid secretion. The orexin receptors are distributed within the hypothalamus, and expression of orexin-1 receptors (OX1R) is greatest in the anterior hypothalamus and ventromedial nucleus. Therefore, we hypothesised that ventromedial hypothalamic OX1R may be involved in the control of gastric acid secretion. To address this question, we examined the effects of orexin-A and a selective OX1R antagonist, SB-3345867, on gastric acid secretion in pyloric-ligated conscious rats. Intraventromedial injection of orexin-A (0.5,2 ,g/,l) stimulated gastric acid secretion in a dose-dependent manner. This stimulatory effect of orexin-A persisted over 3 h. In some experiments, SB-3345867 (10 mg/kg i.p.) was administered 30 min before orexin-A or saline injections. We found that i.p. injection of SB-334867 suppressed stimulated gastric acid secretion induced by orexin-A (2 ,g/,l). Atropine (5 mg/kg) also inhibited the stimulatory effect of central injection of orexin-A on acid secretion. In conclusion, the present study suggests that endogenous orexin-A acts on the ventromedial hypothalamus to stimulates acid secretion. This stimulatory effect is probably mediated through OX1R. [source]

    Nerve Growth Factor Secretion in Cultured Enteric Glia Cells is Modulated by Proinflammatory Cytokines

    G. B. T. Von Boyen
    The enteric nervous system is composed of neurones and glial cells. These enteric glia cells (EGC) appear to be essential for the maintenance of gut homeostasis and mucosal integrity. Neurotrophin nerve growth factor (NGF) also plays an important role for the gut integrity by regulating sensory and inflammatory processes in the intestines. Here, we demonstrate EGCs as one source of NGF and show increased levels of NGF mRNA/protein and tropomyosin receptor kinase A (TrkA) mRNA in cultured EGCs upon stimulation with proinflammatory cytokines and lipopolysaccharides. NGF is continuously secreted from cultured EGCs and proinflammatory cytokines and lipopolysaccharides stimulate the secretion of this neurotrophin in a time- and dose- dependent manner, whereas interleukin-4 had no effect on NGF expression. Furthermore, NGF secretion was sustained for more than 12 h after withdrawal of the proinflammatory cytokines, suggesting the involvement of transcriptional and/or translational processes. Thus, the release of proinflammatory cytokines can increase NGF secretion by EGCs and leads to a higher expression of TrkA in EGCs. NGF, in turn, can increase visceral sensitivity and, on the other hand, appears to improve gut inflammation. Therefore, NGF secreting EGCs may play a key role in modulating visceral sensitivity and might be involved in inflammatory processes of the gut. [source]

    Differential Role of Corticotrophin-Releasing Factor Receptor Types 1 and 2 in Stress-Induced Suppression of Pulsatile Luteinising Hormone Secretion in the Female Rat

    X. F. Li
    Corticotrophin-releasing factor (CRF) plays a pivotal role in stress-induced suppression of the gonadotrophin-releasing hormone pulse generator. We have previously shown that type 2 CRF receptors (CRF2) mediate restraint stress-induced suppression of luteinising hormone (LH) pulses in the rat. The present study aimed: (i) to determine whether type 1 CRF receptors (CRF1) are also involved in this response to restraint and (ii) to investigate the differential involvement of CRF1 and CRF2 in the suppression of LH pulses in response to the metabolic perturbation of insulin-induced hypoglycemia and the innate immunological challenge of lipopolysaccharide (LPS). Ovariectomised rats with oestrogen replacement were implanted with intracerebroventricular (i.c.v.) and intravenous (i.v.) cannulae. Blood samples (25 l) were collected every 5 min for 5 h for LH measurement. After 2 h of controlled blood sampling, rats were either exposed to restraint (1 h) or injected intravenously with insulin (0.25 IU/kg) or LPS (5 g/kg). All three stressors suppressed LH pulses. The CRF1 antagonist SSR125543Q (11.5 mol/rat i.v., 30 min before stressor) blocked the inhibitory response to restraint, but not hypoglycaemia or LPS stress. In addition to its effect on restraint, the CRF2 antagonist astressin2 -B (28 nmol/rat i.c.v., 10 min before insulin or LPS) blocked hypoglycaemia or LPS stress-induced suppression of LH pulses. These results suggest that hypoglycaemia and LPS stress-induced LH suppression involves activation of CRF2 while restraint stress-induced inhibition of LH pulses involves both CRF1 and CRF2. [source]

    Inhibition by Lipopolysaccharide of Naloxone-Induced Luteinising Hormone Secretion Is Accompanied by Increases in Corticotropin-Releasing Factor Immunoreactivity in Hypothalamic Paraventricular Neurones in Female Rats

    D. He
    Abstract We have recently reported that lipopolysaccharide (LPS), a bacterial endotoxin, inhibits steroid-induced as well as naloxone-induced luteinising hormone (LH) secretion in ovariectomised oestrogen-primed rats. In the present study, we examined whether corticotropin-releasing factor (CRF) may be involved in the LPS-induced inhibition of LH secretion. Unanaesthetised rats were treated with an intravenous (i.v.) injection of LPS (10 g) or saline, followed by an i.v. injection of naloxone (20 mg/kg). After sequential blood samples were collected for determination of serum LH concentrations, the brains were fixed and CRF-immunoreactivity was examined histochemically. In control rats receiving saline injections, only a small number of CRF-immunoreactive (ir) cells were found in the parvocellular portion of the hypothalamic paraventricular nucleus (PVN), and naloxone significantly increased serum LH concentrations within 10 min. By contrast, in LPS-treated rats, the number of CRF-ir cells was significantly greater than that in control rats, and the effect of naloxone was completely abolished. In a separate experiment, an intracerebroventricular injection of 5 g CRF inhibited naloxone-induced LH release, mimicking the effect of LPS. These results suggest that LPS stimulates production of CRF in PVN neurones, which in turn inhibits LH secretion without opioidergic mediation. [source]

    Neuropeptide Y (NPY) Delays the Oestrogen-Induced Luteinizing Hormone (LH) Surge in the Ovariectomized Ewe: Further Evidence That NPY has a Predominant Negative Effect on LH Secretion in the Ewe

    K. M. Estrada
    Abstract Studies in rats suggest that neuropeptide Y (NPY) plays a stimulatory role in the generation of the preovulatory luteinizing hormone (LH) surge, via the Y1 receptor. We have investigated this issue using the oestradiol benzoate (EB)-treated ovariectomized (OVX) ewe which is a model for the preovulatory LH surge. A Y1 receptor antagonist (BIBO3304) was infused (25 g/h) into the third cerebral ventricle (III-V) from 2 h before EB injection for 24 h, and had no effect on the ensuing LH surge. Using in situ hybridization, we then examined expression of NPY mRNA in the arcuate nucleus during the luteal, follicular and oestrous phases of the oestrous cycle, and found that levels were greatest during the luteal phase. Thus, reduced NPY synthesis might be an integral factor in the events leading to the cyclic preovulatory LH surge. This was tested by infusion of NPY (25 g/h) into the III-V (as above). The NPY infusion delayed the LH surge until the infusion was ceased. High levels of NPY expression during the luteal phase of the oestrous cycle may be caused by progesterone. Thus, we determined whether NPY cells possess progesterone receptors (PR) and whether progesterone treatment up-regulates NPY mRNA expression in the arcuate nucleus. Immunohistochemistry for NPY and PR was performed in OVX, oestrogen-treated ewes, but no NPY cells of the arcuate nucleus were seen to colocalize PR. In situ hybridization for NPY was performed in OVX and OVX ewes treated with progesterone. There was no significant effect of progesterone treatment on NPY mRNA expression in the arcuate nucleus. We conclude that chronically elevated levels of NPY block the preovulatory surge of gonadotropin-releasing hormone/LH secretion in sheep, but high levels of NPY mRNA expression in the luteal phase of the oestrous cycle cannot be explained by an action of progesterone. [source]

    Evidence That Gonadotropin-Releasing Hormone II Is Not a Physiological Regulator of Gonadotropin Secretion in Mammals

    P. M. Gault
    Abstract Gonadotropin-releasing hormone (GnRH)-II stimulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion when administered at high doses in mammals, and this effect has been assumed to be mediated through the GnRH-II receptor expressed on gonadotropes. This study used two selective GnRH-I receptor antagonists to test the alternative hypothesis that GnRH-II acts through the GnRH-I receptor to elicit gonadotropin secretion. The antagonist, antide, was used to characterize the receptor-relay because it was a pure antagonist in vitro based on inositol phosphate responses in COS-7 cells transfected with either mammalian GnRH-I and GnRH-II receptors and, in vivo, potently antagonized the gonadotropin-releasing effect of a single injection of 250 ng GnRH-I in our sexually inactive sheep model. In a series of studies in sheep, antide (i) blocked the acute LH response to a single injection of GnRH-II (20 g antide: 10 g GnRH-II); (ii) blocked both the acute, pulsatile LH response and the FSH priming response to 2-hourly injections of GnRH-II over 36 h (100 g antide/8 h: 4 g GnRH-II/2 h); and (iii) chronically blocked both the pulsatile LH response and the marked FSH priming response to 4-hourly injections of GnRH-II over 10 days (75 g antide/8 h: 4 g GnRH-II/4 h). In two final experiments, the GnRH-I antagonist 135-18, shown previously to agonize the mammalian GnRH-II receptor, blocked the gonadotropin-releasing effects of GnRH-I (250 ng) but failed to elicit an LH response when given alone, and simultaneous administration of GnRH-II (250 ng) failed to alter the LH-releasing effect of GnRH-I (50,500 ng). These data thus support our hypothesis. Based on additional literature, it is unlikely that the GnRH-II decapeptide is a native regulator of the gonadotrope in mammals. [source]

    Opioid Receptor Subtypes Involved in the Regulation of Prolactin Secretion During Pregnancy and Lactation

    Z. B. Andrews
    Abstract Afferent endogenous opioid neuronal systems facilitate prolactin secretion in a number of physiological conditions including pregnancy and lactation, by decreasing tuberoinfundibular dopamine (TIDA) inhibitory tone. The aim of this study was to investigate the opioid receptor subtypes involved in regulating TIDA neuronal activity and therefore facilitating prolactin secretion during early pregnancy, late pregnancy and lactation in rats. Selective opioid receptor antagonists nor-binaltorphimine (, -receptor antagonist, 15 g/5 l), beta funaltrexamine (, -receptor antagonist, 5 g/5 l) and naltrindole (, -receptor antagonist, 5 g/5 l) or saline were administered intracerebroventricularly (i.c.v.) on day 8 of pregnancy during a nocturnal prolactin surge, on day 21 of pregnancy during the ante partum prolactin surge or on day 7 of lactation before the onset of a suckling stimulus. Serial blood samples were collected at regular time intervals, via chronic indwelling jugular cannulae, before and after drug administration and plasma prolactin was determined by radioimmunoassay. TIDA neuronal activity was measured using the 3,4-dihydroxyphenylacetic acid (DOPAC) : dopamine ratio in the median eminence 2 h 30 min after i.c.v. drug injection. In each experimental condition, plasma prolactin was significantly inhibited by both , - and , -receptor antagonists, whereas the , -receptor antagonist had no effect compared to saline-injected controls. Similarly, nor-binaltorphimine and beta funaltrexamine significantly increased the median eminence DOPAC : dopamine ratio during early and late pregnancy, and lactation whereas naltrindole had no effect compared to saline-injected controls. These data suggest that TIDA neuronal activity, and subsequent prolactin secretion, is regulated by endogenous opioid peptides acting at both , - and , -opioid receptors during prolactin surges of early pregnancy, late pregnancy and lactation. [source]