CONTROL OF IL-6 EXPRESSION AND RESPONSE IN FIBROBLASTS FROM PATIENTS WITH SYSTEMIC-SCLEROSIS

被引：44

作者：

FEGHALI, CA ^{[1
]}

BOST, KL ^{[1
]}

BOULWARE, DW ^{[1
]}

LEVY, LS ^{[1
]}

机构：

[1] TULANE UNIV,SCH MED,DEPT MED,NEW ORLEANS,LA 70112

来源：

AUTOIMMUNITY | 1994年 / 17卷 / 04期

关键词：

SCLERODERMA; FIBROBLAST; INTERLEUKIN-6; TRANSCRIPTION;

D O I：

10.3109/08916939409010671

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Systemic sclerosis (SSc) is an autoimmune connective tissue disease of unknown etiology in which aberrant fibroblast Function results in fibrosis of the skin and internal organs. A distinguishing feature of dermal fibroblasts cultured from SSc lesions is that they produce constitutively, i.e., without exogenous stimulation, as much as 30-fold more interleukin-6 (IL-6) than do normal fibroblasts. The present study indicates that the mechanism of constitutive IL-6 secretion involves the accumulation of IL-6 mRNA in affected SSc fibroblasts, mediated by the constitutive binding of nuclear factors to the IL-6 promoter. DNA-protein complexes formed using nuclear extracts of constitutively expressing cells are distinct from those using extracts of normal cells, with or without exogenous stimulation of IL-6; thus, the mechanisms which regulate constitutive and inducible IL-6 gene expression are apparently distinct. The data also demonstrate that dermal fibroblasts respond very rapidly to IL-6 by increasing expression of the IL-6 gene, thus suggesting a mechanism for the establishment and/or persistence of constitutive expression. The constitutive secretion of IL-6 may play an important role in the perpetuation of the local immune dysregulation and fibroblast activation in the SSc lesion.

引用

页码：309 / 318

页数：10

共 34 条

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