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Epithelial Repair (epithelial + repair)
Selected AbstractsMechanisms 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] Expression of MMP-9, MMP-10 and TNF-, and lack of epithelial MMP-1 and MMP-26 characterize pyoderma gangrenosumJOURNAL OF CUTANEOUS PATHOLOGY, Issue 12 2007Ville Bister Background:, Pyoderma gangrenosum (PG) is a non-infectious, autoimmune, chronic ulcer of the skin, often co-existing with inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) have been implicated as mediators of tissue destruction in chronic cutaneous and intestinal wounds. Methods:, Twenty-four skin biopsies with clinically and histologically confirmed PG and acute wounds were immunostained for MMP-1, -7, -8, -9, -10 and -26; tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -3 and tumor necrosis factor-, (TNF-,). Results:, MMP-1 was generally expressed by keratinocytes distal from the wound edge, whereas MMP-10 was detected abundantly in the epithelium. MMP-26 was positive in 42% at the migratory front. Abundant stromal expression was evident for MMP-1, -9 and -10, TIMP-1 and -3 and TNF-,. In acute wounds, stromal MMP-1, -9 and -10 and TNF-, were sparse. Conclusions:, Unlike in normally healing cutaneous wounds, MMP-1 and -26 were detected bordering the wound in only a minority of PGs and their lack may thus retard epithelial repair. Particularly, MMP-9 and -10 and TNF-, would be suitable therapeutic targets as they may contribute to the degradation of provisional matrices needed for migration in healing wounds. The presence of MMP-1, -9, -10 and -26 in both PG and IBD ulcers may suggest a similar pathogenesis for cutaneous and mucosal inflammation. [source] Ethanol Treatment Reduces Bovine Bronchial Epithelial Cell MigrationALCOHOLISM, Issue 4 2005John R. Spurzem Background: Chronic ethanol abuse is associated with significant lung disease. Excessive alcohol intake increases risk for a variety of respiratory tract diseases, including pneumonia and bronchitis. Damage to airway epithelium is critical to the pathogenesis of airway disorders such as chronic bronchitis and chronic obstructive pulmonary disease. The ability of the airway epithelium to repair itself is an important step in the resolution of airway inflammation and disease. Ethanol exposure is known to modulate signaling systems in bronchial epithelial cells. We hypothesize that chronic ethanol exposure down-regulates the adenosine 3,:5,-cyclic monophosphate signaling cascade in airway epithelial cells, resulting in decreased epithelial cell migration and repair. Methods: We evaluated the effect of ethanol on primary cultures of bovine bronchial epithelial cells in in vitro models of cell migration, wound repair, cell attachment, and cell spreading. Results: Ethanol causes a concentration-dependent effect on closure of mechanical wounds in cell monolayers. Pretreatment of cells with 100 mm ethanol for 24 hr further slows wound closure. Ethanol pretreatment also reduced the protein kinase A response to wounding and made the cells unresponsive to stimuli of protein kinase A that accelerate wound closure. The effects of ethanol on cell migration in wound closure were confirmed in another assay of migration, the Boyden chamber cell migration assay. Prolonged treatment with ethanol also reduced other cell functions, such as spreading and attachment, which are necessary for epithelial repair. Conclusions: Ethanol modulates signaling systems that are relevant to airway injury and repair, suggesting that chronic, heavy ethanol ingestion has a detrimental impact on airway repair. Impaired response to inflammation and injury may contribute to chronic airway disease. [source] Inflammation and Epithelial to Mesenchymal Transition in Lung Transplant Recipients: Role in Dysregulated Epithelial Wound RepairAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010L. A. Borthwick Epithelial to mesenchymal transition (EMT) has been implicated in the pathogenesis of obliterative bronchiolitis (OB) after lung transplant. Although TNF-, accentuates TGF-,1 driven EMT in primary human bronchial epithelial cells (PBECs), we hypothesized that other acute pro-inflammatory cytokines elevated in the airways of patients with OB may also accentuate EMT and contribute to dysregulated epithelial wound repair. PBECs from lung transplant recipients were stimulated with TGF-,1 ± IL-1,, IL-8, TNF-, or activated macrophages in co-culture and EMT assessed. The quality and rate of wound closure in a standardized model of lung epithelial injury was assessed in response to above stimuli. Co-treatment with TGF-,1 + TNF-, or IL-1, significantly accentuates phenotypic and some functional features of EMT compared to TGF-,1 alone. Co-treatment with TGF-,1 + TNF-, or IL-1, accelerates epithelial wound closure however the quality of repair is highly dysregulated. Co-treatment with TGF-,1 + IL-8 has no significant effect on EMT or the speed or quality of wound healing. Activated macrophages dramatically accentuate TGF-,1-driven EMT and cause dysregulated wound repair. Crosstalk between macrophage-derived acute inflammation in the airway and elevated TGF-,1 may favor dysregulated airway epithelial repair and fibrosis in the lung allograft via EMT. [source] Sweet talking,cellular carbohydrates and epithelial repairCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2006P. M. Lackie No abstract is available for this article. [source] | ||||||||||