Regulation of human lung fibroblast C1q-receptors by transforming growth factor-beta and tumor necrosis factor-alpha

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 coll agen (cC1q-R) and globular (gC1q-R) domains of C1q and on type I collagen i n human lung fibroblasts. Two fibroblast subpolulations differing in C1q re ceptor expression were obtained by culturing human lung explants in medium containing fresh human serum and heated plasma-derived serum and separating them based on Clq binding [Narayanan, Lurton and Raghu: Bm 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 leve ls of mRNA were assessed by in situ hybridization and Northern analysis, an d 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 le sser extent in both cells. These increases were not reflected in protein le vels of CC1q-R and gC1q-R, which were similar to or less than controls. Bot h IGF-beta and TNF-alpha also increased procollagen [I] mRNA levels in both cells. Overall, TNF-alpha caused a greater increase and the degree of resp onse by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL ce lls. These results indicated that TGF-beta and TNF-alpha upregulate the mRN A levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA le vels significantly. They also indicated different subsets of human lung fib roblasts respond differently to inflammatory mediators.