title: Regulation of human lung fibroblast C1q-receptors by transforming growth factor-beta and tumor necrosis factor-alpha.
abstract: Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are two polypeptide mediators which are believed to play a role in the evolution of idiopathic pulmonary fibrosis (IPF). We have evaluated the effect of these two substances on the expression of receptors for collagen (cC1q-R) and globular (gC1q-R) domains of C1q and on type I collagen in human lung fibroblasts. Two fibroblast subpopulations differing in C1q receptor expression were obtained by culturing human lung explants in medium containing fresh human serum and heated plasma-derived serum and separating them based on C1q binding [Narayanan, Lurton and Raghu: Am J Resp Cell Mol Biol. 1998; 17:84]. The cells, referred to as HH and NL cells, respectively, were exposed to TGF-beta and TNF-alpha in serum-free conditions. The levels of mRNA were assessed by in situ hybridization and Northern analysis, and protein levels compared after SDS-polyacrylamide gel electrophoresis and Western blotting. NL cells exposed to TGF-beta and TNF-alpha contained 1.4 and 1.6 times as much cC1q-R mRNA, respectively, whereas in HH cells cC1q-R mRNA increased 2.0- and 2.4-fold. The gC1q-R mRNA levels increased to a lesser extent in both cells. These increases were not reflected in protein levels of CC1q-R and gC1q-R, which were similar to or less than controls. Both TGF-beta and TNF-alpha also increased procollagen [I] mRNA levels in both cells. Overall, TNF-alpha caused a greater increase and the degree of response by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL cells. These results indicated that TGF-beta and TNF-alpha upregulate the mRNA levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA levels significantly. They also indicated different subsets of human lung fibroblasts respond differently to inflammatory mediators.
authors: Department of Medicine, University of Washington School of Medicine, Seattle, USA.
authors: J
authors: J
authors: Lurton
authors: H
authors: H
authors: Soto
authors: A S
authors: AS
authors: Narayanan
authors: G
authors: G
authors: Raghu
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors; D017403:In Situ Hybridization; D008168:Lung / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D011951:Receptors, Complement; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C032402:complement 1q receptor