Endogenous IL-1alpha from systemic sclerosis fibroblasts induces IL-6 and PDGF-A. Academic Article uri icon

Overview

abstract

  • It is reported that fibroblasts derived from clinically affected skin areas of patients with systemic sclerosis (SSc) have the ability to overproduce several cytokines and growth factors (i.e., IL-6, PDGF), an ability that might be involved in the pathogenesis of SSc. We have previously shown that the expression of IL-1alpha was constitutively observed in SSc fibroblasts, whereas this was not detected in normal fibroblasts. Although it was suggested that the aberrant IL-1alpha production could be associated with the fibrogenic phenotype of SSc fibroblasts, little is known about the roles of IL-1alpha in SSc fibroblasts. IL-1alpha induced IL-6 and PDGF-A, which are potent stimulators of collagen production and proliferation in normal fibroblasts. This article examines the proposal that IL-6 and PDGF-A are elevated through the action of endogenous IL-1alpha in SSc fibroblasts. An antisense oligodeoxynucleotide complementary to IL-1alpha mRNA was used to suppress endogenous IL-1alpha. Inhibition of endogenous IL-1alpha led to decreased levels of IL-6 and PDGF-A expression in SSc fibroblasts. Moreover, the blocking of the IL-6 response using anti-IL-6 antibody resulted in a significant reduction of procollagen type I in cultured SSc fibroblasts. These results suggest that endogenous IL-1alpha expressed by SSc fibroblasts may play a key role in the abnormal function of SSc fibroblasts through the expression of IL-6 and PDGF-A.

publication date

  • May 1, 1999

Research

keywords

  • Interleukin-1
  • Interleukin-6
  • Platelet-Derived Growth Factor
  • Scleroderma, Systemic

Identity

PubMed Central ID

  • PMC408350

Scopus Document Identifier

  • 0033121274

Digital Object Identifier (DOI)

  • 10.1172/JCI4304

PubMed ID

  • 10225968

Additional Document Info

volume

  • 103

issue

  • 9