Interleukin‐1β 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.

Increased levels of osteopontin in sputum supernatant in severe refractory asthma

“…In accordance with our finding, a previous study showed that no OPN expression was found in tissue sections of a limited number of non-asthmatic control subjects 6. Previous in vitro studies have shown that OPN is produced by fibroblasts as well as by several murine immune cell types such as macrophages, T cells, B cells and mast cells 13 26 27. We were unable to identify the cells responsible for OPN production in the current study since the inflammatory cells assessed by induced sputum reflect the cellular content of the lower airway lining fluid and not the subepithelial layers that seem to represent the basic cellular source of OPN 6 15…”

Plant Glycoprotein Modulates the Expression of Interleukin-1βviaInhibition of MAP Kinase in HMC-1 Cells

“…26) Consequently, it promotes inflammation, leukocyte infiltration, granuloma formation, and tissue fibrosis. 27) Our results indicate that DBD glycoprotein inhibited the expression of IL-1 and COX-2 and the production of nitric oxide in PMACI-stimulated HMC-1 cells, suggesting its antiinflammatory properties. Recently, it has been found that both COX-2 and inducible NOS (iNOS) play important roles in various inflammatory diseases.…”

Phytoglycoprotein (75 kDa) inhibits expression of interleukin‐1β stimulated by DEHP in human mast cells

“…25,26 Consequently, they promote inflammation, Figure 2. Inhibitory effect of CTB glycoprotein on the phosphorylation of ERK1/2 and p38 MAPK in DHEP (100 mM) stimulated HMC-1 Cells.…”

“…C, control leukocyte infiltration granuloma formation, and tissue fibrosis. 26 In addition, COX-2 is an inducible enzyme found at low concentrations in healthy tissues, but its expression becomes elevated in response to tissue damage during inflammation. Several studies have reported that PGD2, which is the major COX-2 metabolite released from activated mast cells, stimulates the pathogenesis of eosinophilic airway inflammation.…”