Human keratinocytes produce the complement inhibitor factor I: Synthesis is regulated by interferon-gamma. 2007

Krisztina K Timár, and Sami Junnikkala, and Attila Dallos, and Hanna Jarva, and Zahurul A Bhuiyan, and Seppo Meri, and Jan D Bos, and Syed S Asghar
Department of Dermatology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. k.k.timar@amc.uva.nl

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.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014176 Protein Biosynthesis The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS. Genetic Translation,Peptide Biosynthesis, Ribosomal,Protein Translation,Translation, Genetic,Protein Biosynthesis, Ribosomal,Protein Synthesis, Ribosomal,Ribosomal Peptide Biosynthesis,mRNA Translation,Biosynthesis, Protein,Biosynthesis, Ribosomal Peptide,Biosynthesis, Ribosomal Protein,Genetic Translations,Ribosomal Protein Biosynthesis,Ribosomal Protein Synthesis,Synthesis, Ribosomal Protein,Translation, Protein,Translation, mRNA,mRNA Translations
D015603 Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Keratinocyte
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D017244 Complement Factor I A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator. C3b Inactivator,C3b-C4b Inactivator,C4b-C3b-INA,C4bC3bINA,Complement 3b-Complement 4b Inactivator,Complement C4b-C3b Inactivator,C3b C4b Inactivator,C4b C3b INA,C4b-C3b Inactivator, Complement,Complement 3b Complement 4b Inactivator,Complement C4b C3b Inactivator,Inactivator, C3b,Inactivator, C3b-C4b,Inactivator, Complement C4b-C3b

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