Secretory component (polymeric immunoglobulin receptor) as an intrinsic inhibitor of biological functions of interferon gamma in keratinocytes.
Secretory component (SC) acts as a transmembrane polymeric immunoglobulin receptor of epithelial cells and is known to bind to polymeric IgA and to contribute to the secretion of secretory IgA (sIgA). We describe a new biological function for free SC (FSC) by which the expression of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR induced by interferon gamma (IFN gamma) is inhibited in human keratinocytes. This activity coincided with suppression of adenosine cyclic 3,5-monophosphate (cyclic AMP) production in keratinocytes. Keratinocytes produced SC after stimulation with IFN gamma and this production was suppressed by the addition of H-7 or propranolol. The addition of propranolol resulted in prolongation of ICAM-1 expression on keratinocytes induced by IFN gamma. These results suggest that endogenously produced SC, as well as exogenously added FSC, acts as an inhibitor of IFN gamma. Therefore, our results suggest that SC plays an antiinflammatory role in the pathogenesis of inflammatory skin diseases via inhibition in keratinocytes of IFN gamma induced expression of ICAM-1 and HLA-DR.
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D015603:Keratinocytes / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism*; D012635:Secretory Component / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D006684:HLA-DR Antigens; D019056:Receptors, Polymeric Immunoglobulin; D012635:Secretory Component; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D011433:Propranolol; D000242:Cyclic AMP