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Epithelial Barrier (epithelial + barrier)
Terms modified by Epithelial Barrier Selected AbstractsAnalysis of the sinusitis nasal lavage fluid proteome using capillary liquid chromatography interfaced to electrospray ionization-quadrupole time of flight- tandem mass spectrometryELECTROPHORESIS, Issue 9 2004Begona Casado Abstract The nasal lavage fluids (NLFs) from four subjects with acute sinusitis were analyzed to investigate the amount of proteins expressed in this pathology at the beginning of the event (day 1) and after 6 days of treatment with antibiotics and a nasal steroid spray. The protein identification was performed with capillary liquid chromatography-electrospray-quadrupole time of flight-(LC-ESI-Q-TOF)-mass spectrometry. The samples collected on the first day contained high-abundant plasma proteins, such as albumin and immunoglobulins, glandular serous cell proteins (lysozyme, lactoferrin, and polymeric immunoglobulin receptor), epithelial keratins, and inflammatory cell proteins (myeloperoxidase, IL-16, and IL-17E). After six days of therapy, the complexity of the proteome was reduced to plasma proteins and lysozyme with no inflammatory markers. The presence of hemoglobin, however, suggested that significant squamous metaplasia with breaches in the epithelial barrier, or nasal steroid-related bleeding, had occurred. The proteomic approach presented here allowed us to identify, in the high complexity of acute sinusitis nasal secretions, the proteins that respond to a pharmacological treatment and that could be suitable as markers of this pathology. [source] TLR2-independent induction and regulation of chronic intestinal inflammationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2010Olivier Boulard Abstract Interactions between the intestinal microflora and host innate immune receptors play a critical role in intestinal homeostasis. Several studies have shown that TLR2 can modulate inflammatory responses in the gut. TLR2 signals enhance tight junction formation and fortify the epithelial barrier, and may play a crucial role in driving acute inflammatory responses towards intestinal bacterial pathogens. In addition, TLR2 agonists can have direct effects on both Th1 cells and Treg. To define the role of TLR2 in the induction and regulation of chronic intestinal inflammation we examined the effects of TLR2 deletion on several complementary models of inflammatory bowel disease. Our results show that TLR2 signals are not required for the induction of chronic intestinal inflammation by either innate or adaptive immune responses. We further show that TLR2,/, mice harbor normal numbers of Foxp3+ Treg that are able to suppress intestinal inflammation as effectively as their WT counterparts. We also did not find any intrinsic role for TLR2 for pathogenic effector T-cell responses in the gut. Thus, in contrast to their role in acute intestinal inflammation and repair, TLR2 signals may have a limited impact on the induction and regulation of chronic intestinal inflammation. [source] Differential expression of antimicrobial peptides in margins of chronic woundsEXPERIMENTAL DERMATOLOGY, Issue 7 2010Stefanie Dressel Please cite this paper as: Differential expression of antimicrobial peptides in margins of chronic wounds. Experimental Dermatology 2010; 19: 628,632. Abstract:, Skin wounds usually heal without major infections, although the loss of the mechanical epithelial barrier exposes the tissue to various bacteria. One reason may be the expression of antimicrobial peptides (AMP) of which some [human ,-defensins (hBD) and LL-37] were recently shown to support additionally certain steps of wound healing. There are no studies which have compared expression patterns of different classes of AMP in chronic wounds. The aim of our study was therefore to analyse the expression profile of hBD-2, hBD-3, LL-37, psoriasin and RNase 7 by immunohistochemistry from defined wound margins of chronic venous ulcers. We detected a strong induction of psoriasin and hBD-2 in chronic wounds in comparison with healthy skin. Except for stratum corneum, no expression of RNase 7 and LL-37 was detected in the epidermis while expression of hBD-3 was heterogeneous. Bacterial swabs identified Staphylococcus aureus and additional bacterial populations, but no association between colonization and AMP expression was found. The differential expression of AMP is noteworthy considering the high bacterial load of chronic ulcers. Clinically, supplementation of AMP with the capability to enhance wound healing besides restricting bacterial overgrowth could present a physiological support for treatment of disturbed wound healing. [source] Gastrointestinal effects of nonsteroidal anti-inflammatory drugsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2003Brendan J. R. Whittle Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) causes extensive damage to the gastrointestinal (GI) tract. The underlying mechanisms of gastric injury include topical irritant actions that disrupt the epithelial barrier, as well as the inhibition of cyclo-oxygenase (COX), which is predominantly the COX-1 isoform in the mucosa. This damage can be attenuated by antisecretory agents or by mucosal protective agents such as the synthetic prostanoids or nitric oxide (NO) donors. Compounds designed to attenuate topical irritancy, or have protective agents incorporated, such as NO-containing NSAIDs, the CINODs (cyclo-oxygenase-inhibiting NO-donating drugs) show reduced mucosal injury. NSAIDs also cause injury in the small intestine, which appears to result from initial COX inhibition, with subsequent translocation of indigenous bacteria, induction of NO synthase and production of the cytotoxic moiety, peroxynitrite. The COX-2 selective agents, the coxibs, which inhibit prostanoid biosynthesis at inflammatory sites, but not the endogenous protective prostanoids in the gut formed by COX-1, have proved so far to be a successful therapeutic approach to reducing NSAIDs GI damage. The clinical outcome of the use of the second generation of coxibs, and the newer NO NSAIDs is now awaited. [source] Epithelial barrier disruption allows nondisease-causing bacteria to initiate and sustain IBD in the IL-10 gene-deficient mouse,INFLAMMATORY BOWEL DISEASES, Issue 8 2007Beate C. Sydora PhD Abstract Background: In the IL-10 gene-deficient mouse model, development of intestinal inflammation is associated with a defect in epithelial barrier integrity that is thought to allow sufficient passage of bacteria or bacterial antigens to initiate a mucosal immune response. Microbial monoassociation experiments into axenic animals have shown that some, but not all, endogenous bacteria will initiate an intestinal inflammatory response. For instance, Bacteroides vulgatus does not initiate intestinal inflammation in axenic IL-10 gene-deficient mice. We investigated whether B. vulgatus requires concomitant disruption of the intestinal epithelial barrier integrity in order to initiate an inflammatory response. Methods: We first identified a dose of the indomethacin that would cause a primary disruption of the epithelial barrier without causing intestinal inflammation. IL-10 axenic mice were then administered this dose of indomethacin in their drinking water for 7 days and concomitantly monoassociated, by oral gavage, with B. vulgatus. Results: Indomethacin treatment (2 ,g/g/d) for 7 days resulted in disruption of epithelial barrier integrity, but it caused neither a systemic inflammatory response nor a mucosal inflammatory response in the colon or cecum. Monoassociation with B. vulgatus alone did not lead to a mucosal inflammatory response, despite a measurable systemic response. In contrast, administration of indomethacin plus B. vulgatus -monoassociation resulted in a marked intestinal inflammatory response in colon and cecum. Conclusions: Our data show that, in a genetically predisposed animal model, the nondisease-causing endogenous bacteria, B. vulgatus, is able to cause an intestinal inflammatory response provided that disruption of the intestinal epithelial barrier has occurred. (Inflamm Bowel Dis 2007) [source] Mechanisms and modulation of intestinal epithelial repairINFLAMMATORY BOWEL DISEASES, Issue 1 2001Dr. Axel U. Dignass Abstract The mucosal epithelium of the alimentary tract represents a crucial barrier to a broad spectrum of noxious and immunogenic substances within the intestinal lumen. An impairment of the integrity of the mucosal epithelial barrier is observed in the course of various intestinal disorders including inflammatory bowel diseases (IBD), celiac disease, intestinal infections, and various other diseases. Furthermore, even under physiologic conditions temporary damage of the epithelial surface mucosa may be caused by proteases, residential flora, dietary compounds, or other factors. Generally, the integrity of the intestinal mucosal surface barrier is rapidly reestablished even after extensive destruction because of an enormous regenerative capability of the mucosal surface epithelium. Rapid resealing of the surface epithelium is accomplished by epithelial cell migration, also termed epithelial restitution, epithelial cell proliferation, and differentiation. Healing of the intestinal surface epithelium is regulated by a complex network of highly divergent factors, among them a broad spectrum of structurally distinct regulatory peptides that have been identified within the mucosa of the intestinal tract. These regulatory peptides, conventionally designated as growth factors and cytokines, play an essential role in regulating differential epithelial cell functions to preserve normal homeostasis and integrity of the intestinal mucosa. In addition, a number of other peptide molecules such as extracellular matrix factors and blood clotting factors, and also nonpeptide molecules including phospholipids, short-chain fatty acids, adenine nucleotides, trace elements, and pharmacological agents, have been demonstrated to modulate intestinal epithelial repair mechanisms. Some of these molecules may be released by platelets, adjacent stromal cells, inflammatory cells, or injured epithelial and nonepithelial cells and may play an important role in the modulation of intestinal injury. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including IBD and require constant repair of the epithelium. Enhancement of intestinal repair mechanisms by regulatory peptides or other modulatory factors may provide future approaches for the treatment of diseases that are characterized by injuries of the epithelial surface. [source] c-Jun N-terminal kinase is largely involved in the regulation of tricellular tight junctions via tricellulin in human pancreatic duct epithelial cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Takashi Kojima Tricellulin (TRIC) is a tight junction protein at tricellular contacts where three epithelial cells meet, and it is required for the maintenance of the epithelial barrier. To investigate whether TRIC is regulated via a c-Jun N-terminal kinase (JNK) pathway, human pancreatic HPAC cells, highly expressed at tricellular contacts, were exposed to various stimuli such as the JNK activators anisomycin and 12- O -tetradecanoylphorbol 13-acetate (TPA), and the proinflammatory cytokines IL-1,, TNF,, and IL-1,. TRIC expression and the barrier function were moderated by treatment with the JNK activator anisomycin, and suppressed not only by inhibitors of JNK and PKC but also by siRNAs of TRIC. TRIC expression was induced by treatment with the PKC activator TPA and proinflammatory cytokines IL-1,, TNF,, and IL-1,, whereas the changes were inhibited by a JNK inhibitor. Furthermore, in normal human pancreatic duct epithelial cells using hTERT-transfected primary cultured cells, the responses of TRIC expression to the various stimuli were similar to those in HPAC cells. TRIC expression in tricellular tight junctions is strongly regulated together with the barrier function via the JNK transduction pathway. These findings suggest that JNK may be involved in the regulation of tricellular tight junctions including TRIC expression and the barrier function during normal remodeling of epithelial cells, and prevent disruption of the epithelial barrier in inflammation and other disorders in pancreatic duct epithelial cells. J. Cell. Physiol. 225: 720,733, 2010. © 2010 Wiley-Liss, Inc. [source] Microbial induction of CARD15 expression in intestinal epithelial cells via toll-like receptor 5 triggers an antibacterial response loop,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2006B. Begue With the discovery of CARD15 as susceptibility gene for Crohn's disease (CD) a first link to a potential defect in the innate immune system was made. In this work we aimed to analyze enterocyte NOD2/CARD15 expression and regulation in response to bacterial motifs and the consequences of the most common CD-specific CARD15 mutation on antibacterial responses of normal intestinal epithelial cells (IEC). Under normal conditions, IEC lines and ileal enterocytes did not express NOD2/CARD15 mRNA or protein, contrary to IEC derived from inflammatory CD sections. In vitro analyses revealed that the simple contact with non-pathogenic commensal E. Coli K12 was sufficient to induced NOD2/CARD15 mRNA and protein in human IEC (HIEC). We identified bacterial flagellin interacting with TLR5 as major motif in this regulation of NOD2/CARD15. E. Coli mutants not expressing flagellin (,FliC) failed to induce CARD15. Similarly, in HIEC transfected with a plasmid encoding dominant negative TLR5, no CARD15 induction was observed after K12 contact. Isolated TLR2 or TLR4 stimulation had no or only a marginal effect on NOD2/CARD15 expression. NOD2/CARD15 negative HIEC were unresponsive to muramyl dipeptide (MDP), but once NOD2/CARD15 was induced, HIEC and Caco2 cells responded to intra or extracellular MDP presentation with the activation of the NFkB pathway. IEC transfected with the Crohn-specific CARD15 mutant (F3020insC, FS) failed to activate NFkB after MDP-challenge, in contrast to CARD15WT IEC. In response to MDP, IEC induced a massive antibacterial peptide (ABP) response, seen in the apical release of CCL20. This was completely abolished in IEC carrying CARD15FS. These data suggest a critical role of NOD2/CARD15 in the bacterial clearance of the intestinal epithelium while CD-specific mutated NOD2/CARD15 causes an impaired epithelial barrier. J. Cell. Physiol. 209: 241,252, 2006. © 2006 Wiley-Liss, Inc. [source] Permeability studies of alkylamides and caffeic acid conjugates from echinacea using a Caco-2 cell monolayer modelJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2004A. Matthias Summary Background:, Echinacea is composed of three major groups of compounds that are thought to be responsible for stimulation of the immune system , the caffeic acid conjugates, alkylamides and polysaccharides. This study has focussed on the former two classes, as these are the constituents found in ethanolic liquid extracts. Objective:, To investigate the absorption of these two groups of compounds using Caco-2 monolayers, which are a model of the intestinal epithelial barrier. Results:, The caffeic acid conjugates (caftaric acid, echinacoside and cichoric acid) permeated poorly through the Caco-2 monolayers although one potential metabolite, cinnamic acid, diffused readily with an apparent permeability (Papp) of 1 × 10,4 cm/s. Alkylamides were found to diffuse through Caco-2 monolayers with Papp ranging from 3 × 10,6 to 3 × 10,4 cm/s. This diversity in Papp for the different alkylamides correlates to structural variations, with saturation and N-terminal methylation contributing to decreases in Papp. The transport of the alkylamides is not affected by the presence of other constituents and the results for synthetic alkylamides were in line with those for the alkylamides in the echinacea preparation. Conclusion:, Alkylamides but not caffeic acid conjugates are likely to cross the intestinal barrier. [source] Response to soy: T-cell-like reactivity in the intestine of Atlantic salmon, Salmo salar L.JOURNAL OF FISH DISEASES, Issue 1 2007A M Bakke-McKellep Abstract T-cell-mediated hypersensitivity could be central in soybean meal (SBM)-induced intestinal changes in salmon. However, tools for immunohistochemical detection of T cells have been lacking in teleosts, including Atlantic salmon. Application of a specific histochemical protocol allowed demonstration of T-cell-like reactivities in formalin-fixed, paraffin-embedded tissues using an antibody reacting to a conserved region of human CD3, (Dako A0452). Characteristic staining was observed in cells of the thymus as well as distal intestine, skin, gills and spleen. These cells were negative for immunoglobulin M (IgM). Intestinal intraepithelial leucocytes were CD3, positive. During the SBM-induced enteropathy, the mixed inflammatory infiltrate in the lamina propria of the distal intestine included many lymphocytes with a T-cell-like reactivity. Real-time polymerase chain reaction revealed significantly increased expression of a complex polypeptide (CD3pp), CD4 and CD8, (P < 0.05) in the distal intestine of SBM-fed fish compared to fish meal-fed reference fish. Increased reactivity for extracellular IgM in the lamina propria and a positive material between the epithelial cells at the tips of the folds was observed, possibly due to leakage of IgM through an abrogated epithelial barrier. In conclusion, a T-cell-like response appears to be involved in this example of a food-sensitive enteropathy. [source] Establishment and characterization of immortalized human gingival keratinocyte cell linesJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2008S. Gröger Background and Objective:, Primary human keratinocytes are used to analyze the properties of the oral epithelium and the early stages of oral bacterial infections. In vitro, these cells are characterized by their short life span and restricted availability. Approaches for culturing these cells will end after approximately 6,10 passages as a result of entry into apoptosis. For this reason, it is important to generate cell lines suitable for obtaining an unlimited source of cells. Therefore, the aim of the present study was to generate gingival keratinocyte cell lines and to compare their in vitro behaviour with those of primary human gingival keratinocytes. Material and Methods:, Primary human gingival keratinocytes were immortalized with a combination of the human papilloma virus onkoproteins E6 and E7. The pattern of the cytokeratins, involucrin and filaggrin was investigated by intracellular staining using flow cytometry. This method allows quantitative analysis of the expression of a variety of intracellular or extracellular markers. Results:, The immortalized cell lines showed many morphological similarities, expressing a cytokeratin pattern that is comparable with that of primary gingival keratinocytes. Furthermore, they developed transepithelial electrical resistance, which is a marker for the generation of tight junctions. These results indicate that the cells might be able to act as an epithelial barrier, reflecting the reaction of primary human cells. Conclusion:, The establishment of a continuous line of human gingival epithelial cells with functional characteristics of the epithelial barrier provides a valuable in vitro model for using to study the early steps of gingival/periodontal infections. [source] Localized antimicrobial peptide expression in human gingivaJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2001Beverly A. Dale The stratified epithelia of the oral cavity are continually exposed to bacterial challenge that is initially resisted by innate epithelial factors and by the recruitment of neutrophils. Antimicrobial peptides from phagocytes and epithelia contribute to this antimicrobial barrier. Using antibodies and in situ hybridization, we explored antimicrobial peptide expression in the varied epithelia of the periodontium and in cultured gingival epithelial cells. In gingival tissue, mRNA for the ,-defensins, human beta-defensin 1 (hBD-1) and human beta-defensin 2 (hBD-2) was predominately localized in suprabasal stratified epithelium and the peptides were detected in upper epithelial layers consistent with the formation of the stratified epithelial barrier. In cultured epithelial cells, both hBD-1 and -2 peptides were detected only in differentiating, involucrin-positive epithelial cells, although hBD-2 required stimulation by proinflammatory mediators or bacterial products for expression. ,-defensins were not detected in junctional epithelium (JE) that serves as the attachment to the tooth surface. In contrast, ,-defensins and cathelicidin family member LL-37 were detected in polymorphonuclear neutrophils (PMNs) that migrate through the JE, a localization that persists during inflammation, when the JE and surrounding tissue are highly infiltrated with PMNs. Thus, the undifferentiated JE contains exogenously expressed ,-defensins and LL-37, and the stratified epithelium contains endogenously expressed ,-defensins. These findings show that defensins and other antimicrobial peptides are localized in specific sites in the gingiva, are synthesized in different cell types, and are likely to serve different roles in various regions of the periodontium. [source] Hypersensitivity and oral tolerance in the absence of a secretory immune systemALLERGY, Issue 5 2010M. R. Karlsson To cite this article: Karlsson M-R, Johansen F-E, Kahu H, Macpherson A, Brandtzaeg P. Hypersensitivity and oral tolerance in the absence of a secretory immune system. Allergy 2010; 65: 561,570. Abstract Background:, Mucosal immunity protects the epithelial barrier by immune exclusion of foreign antigens and by anti-inflammatory tolerance mechanisms, but there is a continuing debate about the role of secretory immunoglobulins (SIgs), particularly SIgA, in the protection against allergy and other inflammatory diseases. Lack of secretory antibodies may cause immune dysfunction and affect mucosally induced (oral) tolerance against food antigens. Methods:, We used polymeric Ig receptor (pIgR) knockout (KO) mice, which cannot export SIgA or SIgM, to study oral tolerance induction by ovalbumin (OVA) feeding and for parenteral antigen sensitization in the same animal. Results:, Remarkable systemic hyperreactivity was observed in pIgR KO mice, as 50% died after intradermal OVA challenge, which was not seen in similarly sensitized and challenged wild-type (WT) mice. Oral tolerance induced by OVA completely protected the sensitized pIgR KO mice against anaphylaxis and suppressed antibody levels (particularly IgG1) as well as delayed-type hypersensitivity (DTH) to OVA. Delayed-type hypersensitivity to a bystander antigen, human serum albumin, was also suppressed and T-cell proliferation against OVA in vitro was reduced in tolerized compared with non-tolerized pIgR KO mice. This effect was largely mediated by CD25+ T cells. Adoptive transfer of splenic putative regulatory T cells (CD4+ CD25+) obtained from OVA-fed pIgR KO mice to naďve WT mice mediated suppression of DTH against OVA after sensitization of the recipients. Conclusion:, Compensatory regulatory T-cell function becomes critical in pIgR-deficient mice to avoid the potentially catastrophic effects of systemic immune hyperreactivity, presumably resulting from defective secretory antibody-mediated immune exclusion of microbial components. [source] Simulated reflux decreases vocal fold epithelial barrier resistance,,THE LARYNGOSCOPE, Issue 8 2010CF-SLP, Elizabeth Erickson MS Abstract Objectives/Hypothesis: The vocal fold epithelium provides a barrier to the entry of inhaled and systemic challenges. However, the location of the epithelium makes it vulnerable to damage. Past research suggests, but does not directly demonstrate, that exposure to gastric reflux adversely affects the function of the epithelial barrier. Understanding the nature of reflux-induced epithelial barrier dysfunction is necessary to better recognize the mechanisms for vocal fold susceptibility to this disease. Therefore, we examined the effects of physiologically relevant reflux challenges on vocal fold transepithelial resistance and gross epithelial and subepithelial appearance. Study Design: Ex vivo, mixed design with between-group and repeated-measures analyses. Methods: Healthy, native porcine vocal folds (N = 52) were exposed to physiologically relevant acidic pepsin, acid-only, or pepsin-only challenges and examined with electrophysiology and light microscopy. For all challenges, vocal folds exposed to a neutral pH served as control. Results: Acidic pepsin and acid-only challenges, but not pepsin-only or control challenges significantly reduced transepithelial resistance within 30 minutes. Reductions in transepithelial resistance were irreversible. Challenge exposure produced minimal gross changes in vocal fold epithelial or subepithelial appearance as evidenced by light microscopy. Conclusions: These findings demonstrate that acidic environments characteristic of gastric reflux compromise epithelial barrier function without gross structural changes. In healthy, native vocal folds, reductions in transepithelial resistance could reflect reflux-related epithelial disruption. These results might guide the development of pharmacologic and therapeutic recommendations for patients with reflux, such as continued acid-suppression therapy and patient antireflux behavioral education. Laryngoscope, 2010 [source] Receptor-mediated transcytosis of botulinum neurotoxin A through intestinal cell monolayersCELLULAR MICROBIOLOGY, Issue 2 2008Aurélie Couesnon Summary Botulism is mainly acquired by the oral route, and botulinum neurotoxin (BoNT) escapes the gastrointestinal tract by crossing the digestive epithelial barrier prior to gaining access to the nerve endings. Here, we show that biologically active BoNT/A crosses intestinal cell monolayers via a receptor-mediated transcytosis, including a transport inhibition at 4°C and a passage at 37°C in a saturable manner within 30,60 min. BoNT/A passage rate was about 10-fold more efficient through the intestinal crypt cell line m-ICcl2, than through the carcinoma Caco-2 or T84 cells, and was not increased when BoNT/A was associated with the non-toxic proteins (botulinum complex). Like for neuronal cells, BoNT/A binding to intestinal cells was mediated by the half C-terminal domain as tested by fluorescence-activated cytometry and by transcytosis competition assay. A ,double receptor model' has been proposed in which BoNT/A interacts with gangliosides of GD1b and GT1b series as well as SV2 protein. Gangliosides of GD1b and GT1b series and recombinant intravesicular SV2-C domain partially impaired BoNT/A transcytosis, suggesting a putative role of gangliosides and SV2 or a related protein in BoNT/A transcytosis through Caco-2 and m-ICcl2 cells. [source] Suppression of neural activity of bronchial irritant receptors by surface-active phospholipid in comparison with topical drugs commonly prescribed for asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2000Hills Background Much indirect evidence has been put forward previously in support of the concept that surface-active phospholipid (SAPL) normally masks irritant receptors in the lungs and upper respiratory tract; but this physical barrier is deficient in asthmatics, imparting hyperresponsiveness of the bronchoconstrictor reflex. Objective To determine whether exogenous SAPL applied to bronchial mucosa reduces the sensitivity of irritant receptors to a standard challenge used clinically to diagnose asthma and to compare the effects with those of corticosteroids and ,-stimulation. Methods Nerve fibres in the vagi were monitored to record action potentials from irritant receptors identified in the upper airways of rat lungs in response to a methacholine challenge. SAPL in the form of dipalmitoyl phosphatidylcholine (PC) and phosphatidylglycerol (PG) , 7 : 3 PC:PG , was applied as a fine dry powder to enhance surface activity and, hence, chemisorption to epithelium. Comparison was also made with clinical doses of i.v. hydrocortisone and instilled salbutamol together with liquid or solid controls, as appropriate. Results Neural activity of irritant receptors was found to be significantly (P = 0.0018) decreased by topical SAPL by 35.8% in response to a methacholine challenge in contrast to an increase of 11.2% in response to a solid (lactose) control. Instilled salbutamol and i.v. hydrocortisone also decreased responses to the same challenge by 43.4% and 14.7%, respectively, in contrast to a liquid (saline) control which increased by 24.5%. Conclusions Surface-active phospholipid has an appreciable effect upon irritant receptors in rat airways, reducing neural response to a methacholine challenge by an amount comparable to that of Salbutamol. These results support the concept of SAPL masking bronchial irritant receptors and warrant placebo-controlled clinical trials of this dry powder as a means of controlling asthma without the side-effects of current medication. Other possible roles discussed for the SAPL epithelial barrier include the exclusion of viruses and allergens. [source] Putative dual role of ephrin-Eph receptor interactions in inflammationIUBMB LIFE, Issue 7 2006Andrei I. Ivanov Abstract Inflammation is associated with a decreased adhesion between endothelial cells in blood vessels and an increased adhesion of circulating leukocytes to vascular endothelium and to epithelia of internal organs. These changes lead to leukocyte extravasation and tissue transmigration. We propose that ephrins and Eph receptors play important, but underappreciated, signaling roles in these processes. At early stages of inflammation, EphA2 receptor and ephrin-B2 are overexpressed in endothelial and epithelial cells, thus leading to those events (expression of adhesion molecules on the cell surface and reorganization of the intracellular cytoskeleton) that cause cell repulsion and disruption of endothelial and epithelial barriers. At later stages of inflammation, expression of EphA1, EphA3, EphB3, and EphB4 on leukocytes and endothelial cells decreases, thus promoting adhesion of leukocytes to endothelial cells. Taking into consideration the abundance of ephrins and Eph receptors in tissues and the robustness of their signaling effects, the proposed involvement is likely to be substantial and may constitute a novel therapeutic target. iubmb Life, 58: 389-394, 2006 [source] | ||||||||||||||||||||||