Interleukin-1beta induces osteopontin expression in pulmonary fibroblasts.

Abstract:

:Osteopontin is a multifunctional matricellular protein identified as one of the most upregulated genes in pulmonary fibrosis. Experimental animal models have identified early pro-fibrotic cytokines as essential to the pathogenesis of inflammation-induced pulmonary fibrosis. However, the principal sources of osteopontin in the fibroproliferative lung, and the factors responsible for its induction, have not been fully defined. We isolated primary rat lung fibroblasts in culture to examine the expression and regulation of lung fibroblast-derived osteopontin. Our results demonstrate a potent and dramatic increase in osteopontin expression induced by interleukin-1beta (IL-1beta), whereas tumor necrosis factor-alpha, transforming growth factor-beta, and angiotensin II had minimal effect. Stimulation with IL-1beta resulted in the secretion of soluble osteopontin protein. We found that osteopontin expression by IL-1beta was regulated via signaling primarily through the mitogen-activated protein kinase member ERK1/2, partially by p38 MAPK, but not at all by JNK. Finally, the mechanism of IL-1beta increase in osteopontin mRNA requires de novo transcription and translation. In conclusion, we find that osteopontin is expressed by primary lung fibroblasts and is potently upregulated by the early inflammatory and pro-fibrotic cytokine IL-1beta. Activated fibroblasts may be a significant source of osteopontin production during lung fibrogenesis.

journal_name

J Cell Biochem

authors

Serlin DM,Kuang PP,Subramanian M,O'Regan A,Li X,Berman JS,Goldstein RH

doi

10.1002/jcb.20661

subject

Has Abstract

pub_date

2006-02-15 00:00:00

pages

519-29

issue

3

eissn

0730-2312

issn

1097-4644

journal_volume

97

pub_type

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