Endogenous IL-1alpha from systemic sclerosis fibroblasts induces IL-6 and PDGF-A.
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.
Kawaguchi
Y
Y
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.YHK02262@niftyserve.ne.jp
Hara
M
M
Wright
T M
TM
D001483:Base Sequence; D017931:DNA Primers; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D011347:Procollagen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology
D017931:DNA Primers; D007375:Interleukin-1; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D012333:RNA, Messenger