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Serlin, DM,Kuang, PP,Subramanian, M,O'Regan, A,Li, XF,Berman, JS,Goldstein, RH
2006
February
Journal Of Cellular Biochemistry
Interleukin-1 beta induces osteopontin expression in pulmonary fibroblasts
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osteopontin interleukin-1 beta lung fibroblast TRANSFORMING-GROWTH-FACTOR RAT CARDIAC FIBROBLASTS GENE-EXPRESSION CRESCENTIC GLOMERULONEPHRITIS DEFICIENT MICE LUNG FIBROSIS IN-VITRO BLEOMYCIN RECEPTOR KINASE
97
519
529
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-1 beta (IL-1 beta), whereas tumor necrosis factor-a, transforming growth factor-beta, and angiotensin II had minimal effect. Stimulation with IL-1 beta resulted in the secretion of soluble osteopontin protein. We found that osteopontin expression by IL-1 beta 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-1 beta 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-1 beta. Activated fibroblasts may be a significant source of osteopontin production during lung fibrogenesis.
DOI 10.1002/jcb.20661
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