Endogenous IL-1a from systemic sclerosis fibroblasts induces IL-6 and PDGF-A

Yasushi Kawaguchi,Masako Hara, and Timothy M. Wright

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-1 a was constitutively observed in SSc fibroblasts, whereas this was not detected in normal fibroblasts. Although it was suggested that the aberrant IL-1 a production could be associated with the fibrogenic phenotype of SSc fibroblasts, little is known about the roles of IL-1in SSc fibroblasts. IL-1induced 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-1 a in SSc fibroblasts. An antisense oligodeoxynucleotide complementary to IL-1mRNA was used to suppress endogenous IL-1. Inhibition of endogenous IL-1 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-1 a 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.