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Interleukin‐1β induces osteopontin expression in pulmonary fibroblasts
Author(s) -
Serlin David M.,
Kuang Ping Ping,
Subramanian Mangalalaxmy,
O'Regan Anthony,
Li Xinfang,
Berman Jeffrey S.,
Goldstein Ronald H.
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20661
Subject(s) - osteopontin , matricellular protein , cancer research , fibrosis , tumor necrosis factor alpha , downregulation and upregulation , cytokine , fibroblast , biology , medicine , microbiology and biotechnology , immunology , cell culture , extracellular matrix , biochemistry , genetics , gene
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‐1β (IL‐1β), whereas tumor necrosis factor‐α, transforming growth factor‐β, and angiotensin II had minimal effect. Stimulation with IL‐1β resulted in the secretion of soluble osteopontin protein. We found that osteopontin expression by IL‐1β 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‐1β 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‐1β. Activated fibroblasts may be a significant source of osteopontin production during lung fibrogenesis. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.