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Increased Secretion (increased + secretion)
Selected AbstractsHormetic effects of gamma radiation on the stress axis of natural populations of meadow voles (Microtus pennsylvanicus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2005Rudy Boonstra Abstract We tested the hypothesis that low doses of gamma radiation have beneficial, hormetic effects on the stress axis (the hypothalamic-pituitary-adrenocortical axis) of free-ranging meadow vole populations (Microtus pennsylvanicus). Voles were exposed to chronic gamma radiation from a 137Cs field irradiator. In isolated populations, voles received one of three treatments over a four-year period: Controls (0.19,0.42 ,Gy/h , levels that were 2,5X above background levels [0.1 ,Gy/h] and live-trapped in all years , 1982,1985), low doses (22.6 ,Gy/h , 50,200X background, live-trapped from November 1982,April 1985), or high doses (3,840 ,Gy/h , 40,000X background, live-trapped from November 1983,April 1985). Voles exposed to a low dose had levels of free and total corticosterone that were significantly higher than those in the control or high-dose groups. Differences in response to radiation between the sexes were apparent for maximum corticosterone-binding capacity, with females exposed to low doses having higher binding capacity than control or high-dose females, whereas males exposed to low doses had lower binding capacity than control or high-dose males. Low-dose voles had higher counts of neutrophils than either the controls or high-dose voles; hematocrit was greater in the controls than in irradiated voles. These results indicate that voles display a hormetic response to radiation, wherein low doses of an otherwise harmful agent produce a beneficial effect. The stimulation of the stress axis resulting in the increased secretion of glucocorticoids, which may protect against the excessive actions of the immune and inflammatory responses, may be a key mechanism producing this effect. [source] Specificity of a new lipid mediator produced by testicular and peritoneal macrophages on steroidogenesisINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2000Lukyanenko Macrophage-derived factor (MDF) is a lipophilic factor produced by rat testicular and peritoneal macrophages that maximally stimulates testosterone production by rat Leydig cells through a steroidogenic acute regulatory protein independent mechanism. The purpose of the present study was to determine whether MDF is also produced by human macrophages, and/or if it acts on human steroidogenic cells. We also studied the tissue-specific functions of MDF by determining if it also acts on steroidogenic cells of the ovary and adrenal glands and, if so, does it require new protein synthesis. It was found that MDF was produced by human peritoneal macrophages, and was capable of stimulating human steroidogenic cells. In terms of tissue specificity, it was found that primary cultures of rat adrenocortical cells respond to MDF with increased secretion of aldosterone and corticosterone, as did rat granulosa cells by producing progesterone. MDF acted in the presence of cycloheximide, indicating that it does not require new protein synthesis. These results indicate that MDF may have significant therapeutic potential and provide a basis for future studies concerning its physiological role in humans. These results further suggest that MDF is not only involved in paracrine regulation of Leydig cells, but also has the potential for the local regulation of steroidogenesis in both granulosa and adrenal cortical cells. [source] Milk consumption: aggravating factor of acne and promoter of chronic diseases of Western societiesJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 4 2009Bodo Melnik Summary Consumption of cow's milk and cow's milk protein result in changes of the hormonal axis of insulin, growth hormone and insulin-like growth factor-1(IGF-1) in humans. Milk consumption raises IGF-1 serum levels in the perinatal period, adolescence and adulthood. During puberty with the physiological onset of increased secretion of growth hormone, IGF-1 serum levels increase and are further enhanced by milk consumption. IGF-1 is a potent mitogen; after binding to its receptor in various tissues, it induces cell proliferation and inhibits apoptosis. Keratinocytes and sebocytes, as well as the androgen-synthesizing adrenals and gonads, are stimulated by IGF-1. The epidemic incidence of adolescent acne in Western milk-consuming societies can be explained by the increased insulin- and IGF-1-stimulation of sebaceous glands mediated by milk consumption. Acne can be regarded as a model for chronic Western diseases with pathologically increased IGF-1-stimulation. Many other organs, such as the thymus, bones, all glands, and vascular smooth muscle cells as well as neurons are subject to this abnormally increased hormonal stimulation. The milk-induced change of the IGF-1-axis most likely contributes to the development of fetal macrosomia, induction of atopy, accelerated linear growth, atherosclerosis, carcinogenesis and neurodegenerative diseases. Observations of molecular biology are supported by epidemiologic data and unmask milk consumption as a promoter of chronic diseases of Western societies. [source] Titanium particles induce the immediate early stress responsive chemokines IL-8 and MCP-1 in osteoblastsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2002Elizabeth A. Fritz Abstract Exposure of human osteoblasts to ultrafine titanium (Ti) particles has been shown to alter osteoblast gene expression. We previously reported that Ti particles can increase IL-6 release and suppress the gene expression of procollagens ,1[I] and ,1[III] in human osteoblasts. In this study, we now demonstrate that Ti particles can rapidly induce the chemotactic cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), two immediate early stress responsive chemokines important for the activation and chemotaxis of neutrophils and macrophages, respectively. In MG-63 osteosarcoma cells and bone marrow derived primary osteoblasts Ti particles selectively increased the steady state levels of IL-8 and MCP-1 mRNA in a time and concentration dependent manner. The increased chemokine mRNA correlated with increased secretion of IL-8 and MCP-1 protein. Actinomycin D, a potent RNA polymerase II inhibitor, blocked the Ti particle induction of IL-8 and MCP-1 mRNA expression, whereas cycloheximide, which inhibits protein synthesis, failed to inhibit chemokine gene expression suggesting Ti particles directly target activation of chemokine gene transcription. Consistent with a transcriptional mechanism not involving new protein synthesis, we demonstrate that Ti particles induce the binding of the p65 and p50 subunits of the latent transcription factor NF-,B to the IL-8 gene promoter. Taken together, these data demonstrate that Ti particles can activate transcription of the stress responsive chemokine genes IL-8 and MCP-1 in human osteoblasts. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Increased liver mast cell recruitment in patients with chronic C virus-related hepatitis and histologically documented steatosisJOURNAL OF VIRAL HEPATITIS, Issue 8 2007B. Franceschini Summary., Hepatitis C virus (HCV) is still one of the major causes of chronic viral infection worldwide, and hepatic steatosis is a frequent pathological finding in patients with chronic HCV-related diseases. It is unclear whether the steatosis is associated with host factors or the virus itself, although a consistent relationship has been found between steatosis and a necro-inflammatory reaction with the increased secretion of immuno-regulators. A primary sources of inflammatory mediators are mast cells (MCs) bone marrow-derived cells that are detected in both normal and diseased livers. We determined MC density and correlated it with the fibrosis, inflammatory reaction and steatosis observed in the liver biopsies of patients affected by HCV with or without steatosis. All the histological features were assessed using a computer-aided image analysis system. There was a statistically significant difference in MC density between the HCV-infected patients with and without steatosis, with the lower mean value being detected in those without (P < 0.02). Furthermore, a nonstatistically significant difference in fibrosis and inflammation between the two patient groups was found. In conclusion, this is the first study showing a significant increase in MC density in the tissues of patients with chronic HCV infection and histologically documented steatosis. [source] ORIGINAL ARTICLE: Antiphospholipid Antibodies Induce a Pro-Inflammatory Response in First Trimester Trophoblast Via the TLR4/MyD88 PathwayAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Melissa J. Mulla Problem, Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, pre-eclampsia, and pre-term labor. aPL target the placenta directly by binding to beta2 -glycoprotein I (,2GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved. Method of study, First trimester trophoblast cells were treated with anti-,2GPI monoclonal antibodies and patient-derived aPL, after which cell survival and function was evaluated. Results, We report that anti-,2GPI antibodies trigger an inflammatory response in trophoblast, characterized by increased secretion of interleukin (IL)-8, MCP-1, GRO-,, and IL-1,, and that this occurs in a TLR-4/MyD88-dependent manner. At high concentrations, these antibodies also induce caspase-mediated cell death. This was attenuated upon disabling of the MyD88 pathway, suggesting that anti-,2GPI-induced inflammatory mediators compromise trophoblast survival by acting in an autocrine/paracrine manner. Enhanced IL-8, GRO-,, and IL-1, secretion also occurred when trophoblast cells were incubated with antibodies from patients with antiphospholipid syndrome. Heparin, which acts as a pro-survival factor in human trophoblast, attenuated the anti-,2GPI antibody-mediated cell death, and also the pro-inflammatory response, but only at high concentrations. Conclusion, These findings demonstrate that aPL triggers a placental inflammatory response via the TLR-4/MyD88 pathway, which in turn compromises trophoblast survival. Thus, the TLR-4/MyD88 pathway may provide a new therapeutic target to improve pregnancy outcome in antiphospholipid syndrome patients. [source] Functional consequences of a germline mutation in the leucine-rich repeat domain of NLRP3 identified in an atypical autoinflammatory disorderARTHRITIS & RHEUMATISM, Issue 4 2010Isabelle Jéru Objective To gain insight into the pathophysiology of an atypical familial form of an autoinflammatory disorder, characterized by autosomal-dominant sensorineural hearing loss, systemic inflammation, increased secretion of interleukin-1, (IL-1,), and the absence of any cutaneous manifestations, and to assess the functional consequences of a missense mutation identified in the leucine-rich repeat (LRR) domain of NLRP3. Methods Microsatellite markers were used to test the familial segregation of the NLRP3 locus with the disease phenotype. All NLRP3 exons were screened for mutations by sequencing. Functional assays were performed in HEK 293T cells to determine the effects of mutated (versus normal) NLRP3 proteins on NF-,B activation, caspase 1 signaling, and speck formation. Results A heterozygous NLRP3 missense mutation (p.Tyr859Cys) was identified in exon 6, which encodes the LRR domain of the protein. This mutation was found to segregate with the disease phenotype within the family, and had a moderate activating effect on speck formation and procaspase 1 processing and did not alter the inhibitory properties of NLRP3 on NF-,B signaling. Conclusion This report is the first to describe a familial form of a cryopyrinopathy associated with a mutation outside of exon 3 of NLRP3. This finding, together with the known efficacy of anti,IL-1 treatments in these disorders, underlines the importance of screening all exons of NLRP3 in patients who present with atypical manifestations. In addition, the gain of function associated with this mutation in terms of activation of caspase 1 signaling was consistent with the observed inflammatory phenotype. Therefore, this study of the functional consequences of an LRR mutation sheds new light on the clinical relevance of in vitro assays. [source] Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migrationBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2005M. Fujiwara Summary Background, ,A keloid is a specific skin lesion that expands beyond the boundaries of the original injury as it heals. Histologically, it is characterized by the excessive accumulation of collagen. However, the reasons for the expansion and the invasive nature of keloids remain unknown. Objectives, We evaluated collagen degradation and migration by cultured keloid fibroblasts based on the assumption that these variables were of functional relevance to the expanding and invasive nature of keloid lesions. Methods, Collagen production was investigated by the detection of type 1 collagen (procollagen type 1C peptide: P1P). Matrix metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-2 (gelatinase-A), were investigated as elements of the collagen degradation system. Enzyme immunoassays were performed to measure the production of P1P, MMP-1, MMP-2, and tissue inhibitor of metalloproteinase (TIMP)-1. To assess the production of MMP-2 its gelatinolytic activity was measured by zymography using gelatin-containing gels. The participation of transforming growth factor-,1 (TGF-,1) in the production and degradation of collagen was also investigated. Finally, the migratory activity of keloid fibroblasts was evaluated using a colony dispersion assay. Results, The production of type 1 collagen, MMP-1, MMP-2, and TIMP-1 by keloid fibroblasts was 3-fold, 6-fold, 2·4-fold, and 2-fold greater than that of normal dermal fibroblasts, respectively. Production of P1P was increased when TGF-,1 was added to cultures of keloid fibroblasts, while it was decreased when anti-TGF-,1 antibody was added to the cultures. In contrast, the production of MMP-1 was decreased by the addition of TGF-,1 to cultured keloid fibroblasts, while it was increased when anti-TGF-,1 antibody was added to the cultures. The production of MMP-2 increased after treatment with TGF-,1, but did not change significantly when anti-TGF-,1 antibody was added to the cultures. Production of TIMP-1 did not change significantly when either TGF-,1 or anti-TGF-,1 antibody was added to the cultures. Keloid fibroblasts showed a 2·5-fold increase of migratory activity compared with normal dermal fibroblasts, while the migratory activity of these fibroblasts was reduced to the control level by treatment with a broad-spectrum MMP inhibitor (GM 6001). Conclusions, Cultured keloid fibroblasts showed increased production of collagen and MMPs, and TGF-,1 played a role in this regulation of production. In addition, increased production of MMPs had a role in the high migratory activity of cultured keloid fibroblasts. [source] Dermatological aspects of angiogenesisBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2002P. Velasco Summary Neovascularization is vital for the growth of tumours, providing a lifeline for sustenance and waste disposal. Tumour vessels can grow by sprouting, intussusception or by incorporating bone marrow-derived endothelial precursor cells into growing vessels. Recent advances in vascular biology have identified some key factors that control vascular growth, and have led to the hypothesis that in normal tissues vascular quiescence is maintained by the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli. In contrast, increased secretion of angiogenic factors and the down-regulation of endogenous angiogenesis inhibitors induce tumour angiogenesis. Vascular quiescence in the skin seems to be primarily maintained by a balance between the endogenous angiogenesis inhibitors thrombospondin 1 and thrombospondin 2 and the potent proangiogenic factor vascular endothelial growth factor A. Inhibiting tumour growth by controlling angiogenesis is an intriguing approach with great potential for the treatment of vascular tumours such as haemangioma, Kaposi's sarcoma and solid cutaneous tumours such as squamous cell carcinoma, melanoma and basal cell carcinoma. In this review, the role of angiogenesis and more recent topics such as lymphangiogenesis in cutaneous tumour growth, invasion and metastasis will be discussed. [source] Correlation of Findings on Direct Laryngoscopy and Bronchoscopy With Presence of Extraesophageal Reflux DiseaseTHE LARYNGOSCOPE, Issue 9 2000Michele M. Carr DDS Abstract Objective To determine the correlation between findings at direct laryngoscopy and bronchoscopy and presence of extraesophageal reflux disease (EERD). Study Design Retrospective chart review Methods Operative notes of 155 children undergoing direct laryngoscopy and bronchoscopy between 1996 and 1999 for airway symptoms for whom there was a suspicion of EERD were examined. Gastroesophageal reflux disease (GERD) was considered present if at least one test was positive (including upper GI series, pH probe, gastric scintiscan, or esophageal biopsy). Results A total of 130 (84%) patients had GERD diagnosed. Ninety percent had at least one laryngotracheal abnormality: 83% had an abnormal larynx and 66% had an abnormal trachea. Laryngeal abnormalities in GERD included postglottic edema, 69%; arytenoid edema, 30%; large lingual tonsil, 16%; vocal fold edema, 12%; vocal fold nodule, 12%; ventricular obliteration, 5%; and hypopharyngeal cobblestoning, 3%. Tracheobronchial abnormalities in GERD included tracheal cobblestoning, 33%; blunting of carina, 12.5%; subglottic stenosis, 11%; increased secretions, 11%; and generalized edema or erythema, 5%. The best sensitivity or specificity was obtained by combining postglottic edema, arytenoid edema, and vocal fold edema, resulting in a sensitivity of 75% and a specificity of 67%. Positive predictive value was 100% for the combination of postglottic edema and any vocal fold or ventricular abnormality. Conclusion Laryngoscopy and bronchoscopy can reveal findings with a high positive predictive value for the presence of GERD. Endoscopy of the upper airway in children with clinical signs and symptoms of EERD is a promising tool for diagnosis. [source] | |||||||||||||