Human keratinocytes produce the complement inhibitor factor H: synthesis is regulated by interferon-gamma.
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-1alpha, IL-2, IL-6, TGF-beta1, TNF-alpha and IFN-gamma. 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-gamma but not by other cytokines tested. Western blot analysis revealed that IFN-gamma augments the synthesis of both molecular species, factor H (FH; 155kDa) and factor H-like protein-1 (FHL-1; 45kDa), of factor H. Factor H released in response to IFN-gamma was functionally active. In conclusion, we demonstrate that keratinocytes are capable of synthesizing factor H and that this synthesis is regulated by IFN-gamma.
Timár
Krisztina K
KK
Department of Dermatology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. k.k.timar@amc.uva.nl
Pasch
Marcel C
MC
van den Bosch
Norbert H A
NH
Jarva
Hanna
H
Junnikkala
Sami
S
Meri
Seppo
S
Bos
Jan D
JD
Asghar
Syed S
SS
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017244:Complement Factor I / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D003179:Complement C3b; D017242:Complement Factor H; D007371:Interferon-gamma; D017244:Complement Factor I