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Effects of TGF-beta, TNF-alpha, IL-beta and IL-6 alone or in combination, and tyrosine kinase inhibitor on cyclooxygenase expression, prostaglandin E2 production and bone resorption in mouse calvarial bone cells.
Int J Biochem Cell Biol. 2004 Nov; 36(11):2270-80.IJ

Abstract

Cyclooxygenase-2 (COX-2) and tyrosine kinase, which are involved in the biosynthesis of prostaglandin E(2) (PGE(2)) in mouse calvarial osteoblasts, are stimulated by cytokine interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and/or interleukin-6 (IL-6). IL-1beta and IL-6 and, to a lesser extent, TNF-alpha, enhances COX-2 mRNA levels in calvarial osteoblasts. Simultaneous treatment with IL-6 and IL-1beta and TNF-alpha resulted in enhanced COX-2 mRNA levels accompanied by the cooperative stimulation of PGE(2) biosynthesis compared to cells treated with IL-1beta or TNF-alpha or IL-6 alone. In contrast, the presence of TGF-beta reduced COX-2 mRNA level, PGE(2) biosynthesis and bone resorption induced by IL-1beta, TNF-alpha, IL-6 or a combination thereof. However, neither IL-1beta, TNF-alpha, IL-6 nor a combination of IL-1beta, TNF-alpha, IL-6 enhanced COX-1 mRNA levels in calvarial osteoblasts. A novel Src tyrosine kinase inhibitor, Herbimycin A (HERB), reduced COX-2 mRNA levels as well as PGE(2) production induced by IL-1beta, TNF-alpha and IL-6 or a combination of IL-1beta, TNF-alpha, IL-6, whereas COX-1 mRNA levels remained unaffected. Finally, HERB was found to inhibit in vitro bone resorption. These results indicate that the cooperative effects of IL-beta, TNF-alpha, IL-6 on PGE(2) production are due to the enhanced expression of the COX-2 gene and that tyrosine kinase(s) are involved in COX-2 signal transduction in mouse calvarial osteoblasts. Thus, the Src family of kinase inhibitors may be useful in treating diseases associated with elevated bone loss.

Authors+Show Affiliations

Park YG
Department of Orthodondritics, Kyung-Hee University College of Dental Medicine, Dongdaemun-Ku, Seoul 130-701, South Korea.
Kang SK
No affiliation info available
Kim WJ
No affiliation info available
Lee YC
No affiliation info available
Kim CH
No affiliation info available

MeSH

AnimalsBenzoquinonesBone ResorptionCells, CulturedCyclooxygenase 2CytokinesDinoprostoneEnzyme InhibitorsGene Expression RegulationInterleukin-1Interleukin-6IsoenzymesLactams, MacrocyclicMiceOsteoblastsProstaglandin-Endoperoxide SynthasesQuinonesRNA, MessengerRifabutinSkullTransforming Growth Factor betaTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15313472

Citation

Park, Young-Guk, et al. "Effects of TGF-beta, TNF-alpha, IL-beta and IL-6 Alone or in Combination, and Tyrosine Kinase Inhibitor On Cyclooxygenase Expression, Prostaglandin E2 Production and Bone Resorption in Mouse Calvarial Bone Cells." The International Journal of Biochemistry & Cell Biology, vol. 36, no. 11, 2004, pp. 2270-80.
Park YG, Kang SK, Kim WJ, et al. Effects of TGF-beta, TNF-alpha, IL-beta and IL-6 alone or in combination, and tyrosine kinase inhibitor on cyclooxygenase expression, prostaglandin E2 production and bone resorption in mouse calvarial bone cells. Int J Biochem Cell Biol. 2004;36(11):2270-80.
Park, Y. G., Kang, S. K., Kim, W. J., Lee, Y. C., & Kim, C. H. (2004). Effects of TGF-beta, TNF-alpha, IL-beta and IL-6 alone or in combination, and tyrosine kinase inhibitor on cyclooxygenase expression, prostaglandin E2 production and bone resorption in mouse calvarial bone cells. The International Journal of Biochemistry & Cell Biology, 36(11), 2270-80.
Park YG, et al. Effects of TGF-beta, TNF-alpha, IL-beta and IL-6 Alone or in Combination, and Tyrosine Kinase Inhibitor On Cyclooxygenase Expression, Prostaglandin E2 Production and Bone Resorption in Mouse Calvarial Bone Cells. Int J Biochem Cell Biol. 2004;36(11):2270-80. PubMed PMID: 15313472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of TGF-beta, TNF-alpha, IL-beta and IL-6 alone or in combination, and tyrosine kinase inhibitor on cyclooxygenase expression, prostaglandin E2 production and bone resorption in mouse calvarial bone cells. AU - Park,Young-Guk, AU - Kang,Sung-Koo, AU - Kim,Won-Jin, AU - Lee,Youn-Choon, AU - Kim,Cheorl-Ho, PY - 2003/12/02/received PY - 2004/04/05/revised PY - 2004/04/21/accepted PY - 2004/8/18/pubmed PY - 2005/1/26/medline PY - 2004/8/18/entrez SP - 2270 EP - 80 JF - The international journal of biochemistry & cell biology JO - Int J Biochem Cell Biol VL - 36 IS - 11 N2 - Cyclooxygenase-2 (COX-2) and tyrosine kinase, which are involved in the biosynthesis of prostaglandin E(2) (PGE(2)) in mouse calvarial osteoblasts, are stimulated by cytokine interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and/or interleukin-6 (IL-6). IL-1beta and IL-6 and, to a lesser extent, TNF-alpha, enhances COX-2 mRNA levels in calvarial osteoblasts. Simultaneous treatment with IL-6 and IL-1beta and TNF-alpha resulted in enhanced COX-2 mRNA levels accompanied by the cooperative stimulation of PGE(2) biosynthesis compared to cells treated with IL-1beta or TNF-alpha or IL-6 alone. In contrast, the presence of TGF-beta reduced COX-2 mRNA level, PGE(2) biosynthesis and bone resorption induced by IL-1beta, TNF-alpha, IL-6 or a combination thereof. However, neither IL-1beta, TNF-alpha, IL-6 nor a combination of IL-1beta, TNF-alpha, IL-6 enhanced COX-1 mRNA levels in calvarial osteoblasts. A novel Src tyrosine kinase inhibitor, Herbimycin A (HERB), reduced COX-2 mRNA levels as well as PGE(2) production induced by IL-1beta, TNF-alpha and IL-6 or a combination of IL-1beta, TNF-alpha, IL-6, whereas COX-1 mRNA levels remained unaffected. Finally, HERB was found to inhibit in vitro bone resorption. These results indicate that the cooperative effects of IL-beta, TNF-alpha, IL-6 on PGE(2) production are due to the enhanced expression of the COX-2 gene and that tyrosine kinase(s) are involved in COX-2 signal transduction in mouse calvarial osteoblasts. Thus, the Src family of kinase inhibitors may be useful in treating diseases associated with elevated bone loss. SN - 1357-2725 UR - https://www.unboundmedicine.com/medline/citation/15313472/Effects_of_TGF_beta_TNF_alpha_IL_beta_and_IL_6_alone_or_in_combination_and_tyrosine_kinase_inhibitor_on_cyclooxygenase_expression_prostaglandin_E2_production_and_bone_resorption_in_mouse_calvarial_bone_cells_ DB - PRIME DP - Unbound Medicine ER -