Colorectal polyposis and immune-based therapies: CYTOKINES AS IMMUNE MEDIATORS (Part 6)

In: Colorectal polyposis

4 Sep 2012

 receptors for IL-8

Two receptors for IL-8 have been identified, both of which are members of the G-protein receptor family and are expressed in neutrophils, T cells, monocytes, macrophages, fibroblasts and melanoma cells . IL-13 and IL-4 convert IL-8 into monocyte chemotactic agonists by upregulating receptor expression. IL-8 and related chemokines are thought to aid in recruitment and positioning of mononuclear phagocytes in TH2-dominated responses.

There is some evidence that cytokines exert their immunological effects through the initiation of the cyclooxygenase (COX) pathway. The COX isoenzymes COX-1 and COX-2 are key metabolic enzymes that convert arachidonic acid to PGs. Metabolites of arachidonic acid are essential for numerous immunological and biological processes, including ovulation, inflammation, platelet aggregation and angiogenesis.

COX-1 is constitutively expressed and synthesizes cytoprotec-tive PGs in the gastrointestinal tract. COX-2 is the product of a gene that is expressed in response to growth factors, tumour promoters, or cytokines . The enzyme is inducible by the ras and scr oncogenic cytokines, as well as by IL-1, TGF-P and TNF-a . COX-2 rapidly exerts proinflammatory effects in response to intracellular and external stimuli. Inflammatory stimuli and cytokines induce increased levels of COX-2, which in turn results in the increased production of PGs (PGE2, PGF2). PGE2 increases the blood flow at the site of inflammation, resulting in capillary leakage and the initiation of a cell-mediated immune response. COX-2 has been shown to contribute to T cell development by positively affecting the CD4-/CD8- population and by inducing CD4+ thymocyte development . Overexpression of COX-2 is associated with the stimulation of cellular division and angiogenesis as well as the suppression of apoptosis in cultured epithelial cells.


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