Human keratinocytes produce the complement inhibitor factor H: Synthesis is regulated by interferon-γ

Locally synthesized complement is believed to play an important role in host defense and inflammation at organ level. In the epidermis, keratinocytes have so far been shown to synthesize two complement components, C3 and factor B. Here, we studied the synthesis of factor H by human keratinocytes. We also studied the regulation of factor H synthesis in keratinocytes by several cytokines, namely IL-1α, IL-2, IL-6, TGF-β1, TNF-α and IFN-γ. Human keratinocytes expressed factor H mRNA and constitutively released small amounts of factor H protein into the culture medium. This release was strongly upregulated by IFN-γ but not by other cytokines tested. Western blot analysis revealed that IFN-γ augments the synthesis of both molecular species, factor H (FH; 155 kDa) and factor H-like protein-1 (FHL-1; 45 kDa), of factor H. Factor H released in response to IFN-γ was functionally active. In conclusion, we demonstrate that keratinocytes are capable of synthesizing factor H and that this synthesis is regulated by IFN-γ.