Epithelial cells release proinflammatory cytokines and undergo c-myc-induced apoptosis on exposure to filarial parasitic sheath protein - Bcl2 mediates rescue by activating c-H-ras

Circulating filarial proteins elicit strong immunologic reactions in humans leading to the chronic manifestations in human lymphatic filariasis such a s lymphatic occlusion, fibrosis, edema, and in some cases, tropical pulmona ry eosinophilia. Our earlier studies, in vitro, conclusively prove that fil arial parasitic sheath proteins induce apoptosis in HEp2 cells, an epitheli al cell line, by a pathway inhibitable by bcl2. The present findings provid e evidence that c-myc activation triggers apoptosis in HEp2 cells and that it is also responsible for the burst of abortive proliferation at 6 d of tr eatment of HEp2 bcl2 cells that overexpress bcl2, with filarial parasitic s heath protein, demonstrating the interplay between the two genes c-myc and bcl2, wherein bcl2 acts by restoring the prosurvival signal to c-myc and ke eping its apoptotic tendency in check. This study also indicates that bcl2 upregulates c-H-ras, engaging res to bring about the suppression of apoptos is through protein tyrosine kinase elevation, thus promoting the survival o f the HEp2 bcl2 calls. In addition to the activation of these "signal switc hes," we also observe that these cells release cytokines like IL-6 and IL-8 through the upregulation of c-fos, when exposed to filarial parasitic shea th protein, reflecting on the immunomodulatory capacity of the epithelium t o elicit a host immune response by setting up a chemotactic gradient, attra cting inflammatory cells to die site of infection.