Endogenous IL-1α from systemic sclerosis fibroblasts induces IL-6 and PDGF-A
Yasushi Kawaguchi, Masako Hara, Timothy M. Wright
Yasushi Kawaguchi, Masako Hara, Timothy M. Wright
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Endogenous IL-1α from systemic sclerosis fibroblasts induces IL-6 and PDGF-A

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

Authors

Yasushi Kawaguchi, Masako Hara, Timothy M. Wright

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Figure 1

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(a) Production of IL-1α in affected and unaffected fibroblasts from pati...
(a) Production of IL-1α in affected and unaffected fibroblasts from patients with SSc and in normal fibroblasts. Fibroblasts were cultured in serum-free media for 24 hours, and cell lysates were collected. IL-1α concentrations in cell lysates were measured by an ELISA kit. The results are expressed as the mean ± SD. Asterisks indicate IL-1α concentrations below the sensitivity of the ELISA kit used. (b) Effect of antisense ODN complementary to IL-1α mRNA on IL-1α production in SSc-affected fibroblasts (n = 9). SSc-affected fibroblasts were cultured in serum-free medium with various concentrations of sense (open circles) or antisense (filled circles) ODN for 48 hours. Cell lysates were collected, and IL-1α production was measured using an ELISA kit. The results are expressed as the mean ± SD of IL-1α production. *P < 0.05, **P < 0.01 compared with sense ODN (control) by paired Student’s t test. (c) Time course of IL-1α production in SSc-affected fibroblasts treated with IL-1α antisense ODN. SSc-affected fibroblasts (n = 6) were cultured in serum-free medium with 20 μM of sense (filled bars) or antisense (open bars) ODN for the indicated time. Cell lysates were extracted, and IL-1α production was measured using an ELISA kit. The results are expressed as the mean ± SD of IL-1α production. *P < 0.05 compared with sense ODN (control) by paired Student’s t test.