Role of complements C5, C6 in the pathogenecity of psoriasis

ABSTRACT

Psoriasis lesion/scale contains C5a des Arg and C5b-9 [Takematsu et al., 1992; Terui et al., 2000 and Uyemura et al., 1993]. These activation products may have arisen from C5-C9 produced supposedly by keratinocytes [KC]. In this work we have started with C5 and C6 to prove our hypothesis. Since psoriatic lesions contain several pro-inflammatory cytokines, it is important to find out which pro-inflammatory cytokines can differentially regulate the expected synthesis of C5 and C6 by keratinocytes. Human KC have been cultured in the absence and the presence of varying concentrations of pro-inflammatory cytokines and the synthesis of C components C5 and C6 have been measured by ELISA at the protein level and RT-PCR at the mRNA level. To test whether KC also secrete these C components, the same measurements have been performed to find out if these late components are present in the supernatant of the medium where these KC were cultured. The keratinocytes cell-line A431 was also used and the monocytes cultures were considered as the positive control. The results showed that resting KC synthesize C5 mRNAs in detectable amounts. C5 mRNA which is synthesized by resting KC is not translated into detectable amount of protein. Although resting KC did not produce C6 mRNA in detectable amounts the levels of C6 protein were detectable. However, These C6 protein levels were minimally secreted by resting KC, into the culture medium. TCGF induced the secretion of C5 and C6 while TGF-beta induced only the secretion of C6. Normal KC synthesize their own C5 and C6. The synthesis of them is activated by TCGF. While TGF- 2 activated the synthesis of C6 other factors might be responsible for activating the synthesis of C5. These factors could be secreted from other cell types than KC in human skin