Regulation ofC3andfactor H synthesis ofhumanglomerular mesangial cells byIL-1andinterferon-gamma

SUMMARY Previous reports haveshownproduction ofcomplement components C4,C2andfactor Bbyrenal tissue. We haveshownrecently thathumanproximal tubular epithelial cells (PTEC)synthesize C3in vitro, andthatIL-2enhances thisproduction. Inthepresent study we demonstrate thathuman mesangial cells (MC)inculture produce factor H andthatsupernatants ofactivated peripheral blood mononuclear cells (Tcell growthfactor (TCGF))induceC3 production andenhancefactor H synthesis inbotha time-anddose-dependent manner. To investigate whethercertain defined cytokines fromTCGF were responsible fortheobserved effect, we tested various cytokines fortheir effect on complement production byMC.ItisshownthatIL-Iinduces C3synthesis whereas factor H production isup-regulated byIFN-y, inbotha dose-andtime-dependent manner. Antibody blocking experiments revealed thatC3synthesis induced bybothTCGF andIL-Icouldbeblocked withantibodies specific forIL-1, andalsothatTCGF andIFN-yenhanced factor H synthesis could bothbeblocked withantibodies specific forIFN-y. Cycloheximide was abletoinhibit C3andfactor Hproduction, suggesting denovosynthesis oftheproteins. mRNA-polymerase chainreaction (PCR) analysis revealed mRNA encoding forC3after stimulation withTCGF andIL-1.Factor H genesare constitutively expressed incultured mesangial cells anditsexpression isup-regulated byTCGF and IFN-y. Northern blot analysis withspecific probes forC3andfactor H revealed bandswhichsupport theresults obtained byPCR analysis.