Human keratinocytes produce the complement inhibitor factor I: Synthesis is regulated by interferon-gamma.
Extrahepatic complement synthesis is believed to play an important role in host defense and inflammation at tissue and organ level. In the epidermis the most abundant cell type, keratinocytes have been shown to produce C3, factor B and factor H. In the present study, we investigated the synthesis of factor I by human keratinocytes. We also studied whether proinflammatory cytokines IL-1alpha, IL-6, TGF-beta1, TNF-alpha and IFN-gamma regulate factor I synthesis in keratinocytes. Human keratinocytes constitutively expressed factor I mRNA and produced factor I protein. Amongst the above-mentioned cytokines, only IFN-gamma regulated the synthesis of factor I, and this effect occurred predominantly at pre-translational level. Factor I produced by keratinocytes was functionally active in cleaving C3b. In conclusion, we demonstrate that keratinocytes are capable of synthesizing factor I, 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
Junnikkala
Sami
S
Dallos
Attila
A
Jarva
Hanna
H
Bhuiyan
Zahurul A
ZA
Meri
Seppo
S
Bos
Jan D
JD
Asghar
Syed S
SS
D002478:Cells, Cultured; D017244:Complement Factor I / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins
D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D017244:Complement Factor I