Abstract
The effects of alpha- and gamma-interferons (IFNs) on collagen production by confluent human diploid fibroblasts in culture were examined. It was found that partially purified alpha-IFNs and affinity purified gamma-IFNs caused greater than 50% inhibition of collagen synthesis by these cells independently of their effect on cell proliferation. Recombinant alpha-IFNs showed a similar effect (38.8% inhibition), indicating that collagen synthesis inhibition was a constitutive property of IFNs. Collagen synthesis inhibition by IFNs was concentration dependent. Gel filtration chromatography of the newly synthesized proteins from the media of fibroblasts incubated with partially purified alpha-IFNs demonstrated a selective depression of molecules eluting in the region of procollagen. No detectable increase in collagen degradation products or underhydroxylation of procollagen was observed. Short-term kinetic studies further demonstrated that the major effect of IFNs was due to a net decrease in fibroblast collagen production rather than to impairment of secretion or increased extracellular degradation of the newly synthesized molecules. These results indicate that alpha- and gamma-IFNs are potent inhibitors of human fibroblast collagen production and suggest that they may play an important role in the regulation of normal and pathologic fibrogenesis.
Full text
PDF![1112](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8f/425272/cd36a99f7361/jcinvest00135-0452.png)
![1113](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8f/425272/c5cd50c42787/jcinvest00135-0453.png)
![1114](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8f/425272/01323f2bd046/jcinvest00135-0454.png)
![1115](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8f/425272/604cbfeb3d97/jcinvest00135-0455.png)
![1116](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd8f/425272/8d31d2e91bc5/jcinvest00135-0456.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Hart P. H., Powell L. W., Cooksley W. G., Halliday J. W. Mononuclear cell factors that inhibit fibroblast collagen synthesis. I. In vitro conditions determining their production and expression. Scand J Immunol. 1983 Jul;18(1):41–49. doi: 10.1111/j.1365-3083.1983.tb00834.x. [DOI] [PubMed] [Google Scholar]
- Hibbs M. S., Postlethwaite A. E., Mainardi C. L., Seyer J. M., Kang A. H. Alterations in collagen production in mixed mononuclear leukocyte-fibroblast cultures. J Exp Med. 1983 Jan 1;157(1):47–59. doi: 10.1084/jem.157.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hobbs D. S., Pestka S. Purification and characterization of interferons from a continuous myeloblastic cell line. J Biol Chem. 1982 Apr 25;257(8):4071–4076. [PubMed] [Google Scholar]
- Jimenez S. A., McArthur W., Rosenbloom J. Inhibition of collagen synthesis by mononuclear cell supernates. J Exp Med. 1979 Dec 1;150(6):1421–1431. doi: 10.1084/jem.150.6.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson R. L., Ziff M. Lymphokine stimulation of collagen accumulation. J Clin Invest. 1976 Jul;58(1):240–252. doi: 10.1172/JCI108455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Juva K., Prockop D. J. Modified procedure for the assay of H-3-or C-14-labeled hydroxyproline. Anal Biochem. 1966 Apr;15(1):77–83. doi: 10.1016/0003-2697(66)90249-1. [DOI] [PubMed] [Google Scholar]
- LeRoy E. C. Increased collagen synthesis by scleroderma skin fibroblasts in vitro: a possible defect in the regulation or activation of the scleroderma fibroblast. J Clin Invest. 1974 Oct;54(4):880–889. doi: 10.1172/JCI107827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nielson E. G., Phillips S. M., Jimenez S. Lymphokine modulation of fibroblast proliferation. J Immunol. 1982 Mar;128(3):1484–1486. [PubMed] [Google Scholar]
- Rubinstein S., Familletti P. C., Pestka S. Convenient assay for interferons. J Virol. 1981 Feb;37(2):755–758. doi: 10.1128/jvi.37.2.755-758.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wahl S. M., Wahl L. M., McCarthy J. B. Lymphocyte-mediated activation of fibroblast proliferation and collagen production. J Immunol. 1978 Sep;121(3):942–946. [PubMed] [Google Scholar]