Th1 versus Th2 Inflammation in Mesenchymal Cell Survival and Lung

Th1 versus Th2 Inflammation in Mesenchymal Cell Survival and Lung Fibrosis Even though polypeptide development factors just like PDGF and EGF ligands are vital for sustaining mesenchymal cell survival and proliferation, the survival of those cells can also be determined in massive portion by the type of inflamma tory microenvironment. Within these microenviron ments, mesenchymal cells are bathed inside a selection of cytokines, chemokines and lipid mediators that influence cell survival. Some of these elements that modulate mesenchymal cell survival and phenotype are illustrated in Figure 3. Inflammatory reactions are characterized by the infiltration of mononuclear cells which includes macro phages, lymphocytes, neutrophils and eosinophils. Despite the fact that inflammation normally precedes fibrosis, evi dence from experimental animal models of fibrosis and clinical research where anti inflammatory drugs have little impact on lung fibrosis suggest that inflammation may not be expected for fibrogenesis.
Nonetheless, the concept that inflammation and fibrosis may very well be distinct processes is probably an oversimplification, because it is apparent that inflammatory cytokines and chemokines have potent modulatory effects on development aspect activity. For exam ple, during asthma, infiltrating Th2 lymphocytes pro duce interleukin 13, a crucial cytokine that mediates multiple phenotypes selleck RKI-1447 of airway remodeling, including mucus cell metaplasia, eosinophilia, airway smooth muscle thickening and airway fibrogenesis. IL 13 has also been proposed to play a function in some ani mal models of interstitial lung fibrosis models, including bleomycin and FITC. Transgenic mice that overex press IL 13 create tissue fibrosis via production and activation of TGF b1.
Studies applying a bleomy cin induced pulmonary fibrosis demonstrated that IL 13 signaling via the IL 13a2 receptor is involved in induction of TGF b1 production and fibrosis. The proliferation of lung myofibroblasts in response to IL 13 is mediated by means of the autocrine selelck kinase inhibitor release of PDGF AA and PDGF CC. As illustrated in Figure 3, IL 13 generated through a Th2 inflammatory response is vital in airway and interstitial fibrosis due in component to its capability to increase PDGF and TGF b1, which in turn influence mesenchymal cell survival and collagen deposition. While IL 13 seems to be central towards the patho genesis of airway fibrosis in asthma and in some ani mal models of interstitial fibrosis, other models of lung fibrosis are certainly not dependent on Th2 inflammation and IL 13. For example, V2O5 induced lung fibrosis in mice options Th1 inflammation and elevated levels of interferon g and IFN inducible cytokines along with elevated levels of profibrogenic development aspects and collagen with no apparent increases in IL 13.

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