PMID- 1531292 OWN - NLM STAT- MEDLINE DCOM- 19920311 LR - 20210514 IS - 0264-6021 (Print) IS - 1470-8728 (Electronic) IS - 0264-6021 (Linking) VI - 281 ( Pt 2) IP - Pt 2 DP - 1992 Jan 15 TI - Effect of interferon-gamma on complement gene expression in different cell types. PG - 437-42 AB - We have studied the expression of the complement components C2, C3, factor B, C1 inhibitor (C1-inh), C4-binding protein (C4-bp) and factor H in human peripheral blood monocytes, skin fibroblasts, umbilical vein endothelial cells (HUVEC) and the human hepatoma cell line G2 (Hep G2) in the absence and the presence of interferon-gamma (IFN-gamma). E.l.i.s.a. performed on culture fluids, run-on transcription assays, Northern blot and double-dilution dot-blot techniques confirmed that monocytes expressed all six components, whereas fibroblasts, HUVEC and HepG2 each expressed five of the six components. Fibroblasts and HUVEC did not synthesize C4-bp, and Hep G2 did not produce factor H. In addition to these differences, the synthesis rates of C3, C1-inh and factor H were not the same in all cell types. However, the synthesis rates of C2 and factor B were similar in all four cell types. The half-lives of the mRNAs were shorter in monocytes than in other cell types. Monocyte factor H mRNA had a half-life of 12 min in monocytes, compared with over 3 h in fibroblasts and HUVEC. The instability of factor H mRNA in monocytes may contribute to their low factor H secretion rate. IFN-gamma produced dose-dependent stimulation of C2, factor B, C1-inh, C4-bp and factor H synthesis by all cell types expressing these proteins, but decreased C3 synthesis in all four cell types. Cell-specific differences in the response to IFN-gamma were observed. The increased rates of transcription of the C1-inh and factor H genes in HUVEC were greater than in other cell types, while the increased rate of transcription of the C2, factor B and C1-inh genes in Hep G2 cells was less than in other cell types. IFN-gamma did not affect the stability of C3, factor H or C4 bp mRNAs, but increased the stability of factor B and C1-inh mRNAs and decreased the stability of C2 mRNA. Although these changes occurred in all four cell types studied, the half-life of C1-inh mRNA in monocytes was increased almost 4-fold, whereas the increases in the other cell types were less than 30%. These data show that the constitutive synthesis rates of complement components may vary in the different cell types. They also show that the degree of change in synthesis rates in response to IFN-gamma in each of the cell types often varies due to differences in transcriptional response, sometimes in association with changes in mRNA stability. FAU - Lappin, D F AU - Lappin DF AD - Department of Pathology, Western Infirmary, Glasgow, U.K. FAU - Guc, D AU - Guc D FAU - Hill, A AU - Hill A FAU - McShane, T AU - McShane T FAU - Whaley, K AU - Whaley K LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (CFH protein, human) RN - 0 (Carrier Proteins) RN - 0 (Complement C1 Inactivator Proteins) RN - 0 (Complement C2) RN - 0 (Complement C3) RN - 0 (Complement C3b Inactivator Proteins) RN - 0 (Complement C4) RN - 0 (Integrin alphaXbeta2) RN - 0 (RNA, Messenger) RN - 80295-43-8 (Complement C3b) RN - 80295-65-4 (Complement Factor H) RN - 82115-62-6 (Interferon-gamma) RN - 9007-36-7 (Complement System Proteins) SB - IM MH - Carrier Proteins/genetics/metabolism MH - Cells, Cultured MH - Complement C1 Inactivator Proteins/genetics/metabolism MH - Complement C2/genetics/metabolism MH - Complement C3/genetics/metabolism MH - Complement C3b/genetics/metabolism MH - Complement C3b Inactivator Proteins/genetics/metabolism MH - Complement C4/metabolism MH - Complement Factor H MH - Complement System Proteins/*genetics/metabolism MH - *Gene Expression Regulation MH - Humans MH - Integrin alphaXbeta2 MH - Interferon-gamma/*physiology MH - Kinetics MH - Organ Specificity/genetics MH - RNA, Messenger/metabolism MH - Transcription, Genetic PMC - PMC1130704 EDAT- 1992/01/15 00:00 MHDA- 1992/01/15 00:01 PMCR- 1992/01/15 CRDT- 1992/01/15 00:00 PHST- 1992/01/15 00:00 [pubmed] PHST- 1992/01/15 00:01 [medline] PHST- 1992/01/15 00:00 [entrez] PHST- 1992/01/15 00:00 [pmc-release] AID - 10.1042/bj2810437 [doi] PST - ppublish SO - Biochem J. 1992 Jan 15;281 ( Pt 2)(Pt 2):437-42. doi: 10.1042/bj2810437.