Abstract
We examined IL-1 alpha and IL-1 beta gene expression and protein production in human dermal fibroblasts from patients with systemic sclerosis (SSc) to investigate the abnormal function of SSc fibroblasts. Human dermal fibroblasts were biopsied from 13 patients with SSc, three patients with rheumatoid arthritis (RA) and five healthy normal controls (NC). Cells were cultured in serum-free media and total RNA was collected from second or third passage fibroblasts. In cultured SSc fibroblasts, IL-1 alpha and IL-1 beta mRNAs were constitutively expressed and intracellular pro-IL-1 alpha was present. These observations suggest that an autocrine effect of IL-1 alpha contributes to the fibrosis in SSc.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
- Auron P. E., Warner S. J., Webb A. C., Cannon J. G., Bernheim H. A., McAdam K. J., Rosenwasser L. J., LoPreste G., Mucci S. F., Dinarello C. A. Studies on the molecular nature of human interleukin 1. J Immunol. 1987 Mar 1;138(5):1447–1456. [PubMed] [Google Scholar]
- Barr R. M., Symonds P. H., Akpan A. S., Greaves M. W. Culture of human dermal fibroblasts in collagen gels: modulation of interleukin 1-induced prostaglandin E2 synthesis by an extracellular matrix. Exp Cell Res. 1992 Feb;198(2):321–327. doi: 10.1016/0014-4827(92)90386-m. [DOI] [PubMed] [Google Scholar]
- Dinarello C. A. Interleukin-1 and interleukin-1 antagonism. Blood. 1991 Apr 15;77(8):1627–1652. [PubMed] [Google Scholar]
- Elias J. A., Lentz V. IL-1 and tumor necrosis factor synergistically stimulate fibroblast IL-6 production and stabilize IL-6 messenger RNA. J Immunol. 1990 Jul 1;145(1):161–166. [PubMed] [Google Scholar]
- Elias J. A., Reynolds M. M., Kotloff R. M., Kern J. A. Fibroblast interleukin 1 beta: synergistic stimulation by recombinant interleukin 1 and tumor necrosis factor and posttranscriptional regulation. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6171–6175. doi: 10.1073/pnas.86.16.6171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fuhlbrigge R. C., Fine S. M., Unanue E. R., Chaplin D. D. Expression of membrane interleukin 1 by fibroblasts transfected with murine pro-interleukin 1 alpha cDNA. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5649–5653. doi: 10.1073/pnas.85.15.5649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillis P., Malter J. S. The adenosine-uridine binding factor recognizes the AU-rich elements of cytokine, lymphokine, and oncogene mRNAs. J Biol Chem. 1991 Feb 15;266(5):3172–3177. [PubMed] [Google Scholar]
- Gruschwitz M., Müller P. U., Sepp N., Hofer E., Fontana A., Wick G. Transcription and expression of transforming growth factor type beta in the skin of progressive systemic sclerosis: a mediator of fibrosis? J Invest Dermatol. 1990 Feb;94(2):197–203. doi: 10.1111/1523-1747.ep12874503. [DOI] [PubMed] [Google Scholar]
- Jimenez S. A., Feldman G., Bashey R. I., Bienkowski R., Rosenbloom J. Co-ordinate increase in the expression of type I and type III collagen genes in progressive systemic sclerosis fibroblasts. Biochem J. 1986 Aug 1;237(3):837–843. doi: 10.1042/bj2370837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawaguchi Y., Harigai M., Hara M., Suzuki K., Kawakami M., Ishizuka T., Hidaka T., Kitani A., Kawagoe M., Nakamura H. Increased interleukin 1 receptor, type I, at messenger RNA and protein level in skin fibroblasts from patients with systemic sclerosis. Biochem Biophys Res Commun. 1992 May 15;184(3):1504–1510. doi: 10.1016/s0006-291x(05)80053-1. [DOI] [PubMed] [Google Scholar]
- Kawaguchi Y., Harigai M., Kitani A., Suzuki K., Kawakami M., Ishizuka T., Hidaka T., Hara M., Kawagoe M., Nakamura H. Effect of prolyl 4-hydroxylase inhibitor on fibroblast collagen production in vitro: an approach to the treatment of systemic sclerosis. J Rheumatol. 1992 Nov;19(11):1710–1715. [PubMed] [Google Scholar]
- Kawaguchi Y., Harigai M., Suzuki K., Hara M., Kobayashi K., Ishizuka T., Matsuki Y., Tanaka N., Nakamura H. Interleukin 1 receptor on fibroblasts from systemic sclerosis patients induces excessive functional responses to interleukin 1 beta. Biochem Biophys Res Commun. 1993 Jan 15;190(1):154–161. doi: 10.1006/bbrc.1993.1024. [DOI] [PubMed] [Google Scholar]
- Kawaguchi Y., Kitani A., Hara M., Harigai M., Hirose T., Suzuki K., Kawakami M., Hidaka T., Ishizuka T., Kawagoe M. Cytokine regulation of prolyl 4-hydroxylase production in skin fibroblast cultures from patients with systemic sclerosis: contribution to collagen synthesis and fibrosis. J Rheumatol. 1992 Aug;19(8):1195–1201. [PubMed] [Google Scholar]
- Kumar S., Millis A. J., Baglioni C. Expression of interleukin 1-inducible genes and production of interleukin 1 by aging human fibroblasts. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4683–4687. doi: 10.1073/pnas.89.10.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Last-Barney K., Homon C. A., Faanes R. B., Merluzzi V. J. Synergistic and overlapping activities of tumor necrosis factor-alpha and IL-1. J Immunol. 1988 Jul 15;141(2):527–530. [PubMed] [Google Scholar]
- LeRoy E. C., Black C., Fleischmajer R., Jablonska S., Krieg T., Medsger T. A., Jr, Rowell N., Wollheim F. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988 Feb;15(2):202–205. [PubMed] [Google Scholar]
- Mauviel A., Temime N., Charron D., Loyau G., Pujol J. P. Interleukin-1 alpha and beta induce interleukin-1 beta gene expression in human dermal fibroblasts. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1209–1214. doi: 10.1016/s0006-291x(88)80761-7. [DOI] [PubMed] [Google Scholar]
- Mosley B., Urdal D. L., Prickett K. S., Larsen A., Cosman D., Conlon P. J., Gillis S., Dower S. K. The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor. J Biol Chem. 1987 Mar 5;262(7):2941–2944. [PubMed] [Google Scholar]
- Raines E. W., Dower S. K., Ross R. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science. 1989 Jan 20;243(4889):393–396. doi: 10.1126/science.2783498. [DOI] [PubMed] [Google Scholar]
- Schröder J. M., Sticherling M., Henneicke H. H., Preissner W. C., Christophers E. IL-1 alpha or tumor necrosis factor-alpha stimulate release of three NAP-1/IL-8-related neutrophil chemotactic proteins in human dermal fibroblasts. J Immunol. 1990 Mar 15;144(6):2223–2232. [PubMed] [Google Scholar]
- Takii T., Akahoshi T., Kato K., Hayashi H., Marunouchi T., Onozaki K. Interleukin-1 up-regulates transcription of its own receptor in a human fibroblast cell line TIG-1: role of endogenous PGE2 and cAMP. Eur J Immunol. 1992 May;22(5):1221–1227. doi: 10.1002/eji.1830220517. [DOI] [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trojanowska M., Wu L. T., LeRoy E. C. Elevated expression of c-myc proto-oncogene in scleroderma fibroblasts. Oncogene. 1988 Oct;3(4):477–481. [PubMed] [Google Scholar]
- Wang A. M., Doyle M. V., Mark D. F. Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9717–9721. doi: 10.1073/pnas.86.24.9717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whiteside T. L., Ferrarini M., Hebda P., Buckingham R. B. Heterogeneous synthetic phenotype of cloned scleroderma fibroblasts may be due to aberrant regulation in the synthesis of connective tissues. Arthritis Rheum. 1988 Oct;31(10):1221–1229. doi: 10.1002/art.1780311002. [DOI] [PubMed] [Google Scholar]
- Yamakage A., Kikuchi K., Smith E. A., LeRoy E. C., Trojanowska M. Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts. J Exp Med. 1992 May 1;175(5):1227–1234. doi: 10.1084/jem.175.5.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zucali J. R., Dinarello C. A., Oblon D. J., Gross M. A., Anderson L., Weiner R. S. Interleukin 1 stimulates fibroblasts to produce granulocyte-macrophage colony-stimulating activity and prostaglandin E2. J Clin Invest. 1986 Jun;77(6):1857–1863. doi: 10.1172/JCI112512. [DOI] [PMC free article] [PubMed] [Google Scholar]