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Overproduction of collagen and diminished SOCS1 expression are causally linked in fibroblasts from idiopathic pulmonary fibrosis.

Abstract：

:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal pulmonary disorder, and its pathology is characterized by parenchymal fibrosis. To investigate the characteristics of fibroblasts in IPF, we obtained eight fibroblast cell lines from lungs with IPF and eight lines from normal lungs. We found that the fibroblasts from IPF spontaneously produced higher amounts of type I collagen and had lower expression levels of SOCS1 than fibroblasts from normal lung. By using mouse fibroblasts, we demonstrated the causal relationship between them: the deficiency of SOCS1 in fibroblasts resulted in increased collagen production, whereas overexpression of SOCS1 suppressed collagen production. IFN-gamma suppressed spontaneous collagen production even in SOCS1-deficient fibroblasts, indicating that IFN-gamma inhibition is SOCS1-independent. In contrast, IFN-gamma suppressed the increase of collagen production induced by IL-4 in wild type fibroblasts but not SOCS1-deficient fibroblasts, suggesting IFN-gamma acted exclusively via SOCS1 in this case. Following IFN-gamma stimulation, the amount of SOCS1 mRNA expressed by IPF fibroblasts was comparable to that of normal fibroblasts. Thus, the extent of SOCS1 increase after stimulation by IFN-gamma was significantly higher in IPF fibroblasts. The extent to which IFN-gamma inhibited collagen production was also larger in IPF fibroblasts than in normal fibroblasts. These results suggest that the exaggerated production of collagen observed in fibroblasts from IPF is causally related to the diminished expression of SOCS1, and IPF fibroblasts are more susceptible to IFN-gamma because of decreased expression of SOCS1.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Shoda H,Yokoyama A,Nishino R,Nakashima T,Ishikawa N,Haruta Y,Hattori N,Naka T,Kohno N

doi

10.1016/j.bbrc.2006.12.128

subject

Has Abstract

pub_date

2007-02-23 00:00:00

pages

1004-10

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)02796-3

journal_volume

353

pub_type

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Overproduction of collagen and diminished SOCS1 expression are causally linked in fibroblasts from idiopathic pulmonary fibrosis.