Ectopic Expression of Caveolin-1 Induces COX-2 Expression in Rabbit Articular Chondrocytes via MAP Kinase Pathway

  • Kim, Song-Ja (Department of Biological Sciences, Kongju National University, College of Natural Sciences)
  • 발행 : 2006.09.30

초록

Background: Caveolin-1 is a principal component of caveolae membranes in vivo. Although expression of caveolae structure and expression of caveolin family, caveolin-1, -2 and -3, was known in chondrocytes, the functional role of caveolae and caveolins in chondrocytes remains unknown. In this study, we investigated the role of caveolin-1 in articular chondrocytes. Methods: Rabbit articular chondrocytes were prepared from cartilage slices of 2-week-old New Zealand white rabbits by enzymatic digestion. Caveolin-1 cDNA was transfected to articular chondrocytes using LipofectaminePLUS. The cyclooxygenase-2 (COX-2) expression levels were determined by immunoblot analysis, immunostaining, immunohistochemistry, and prostaglandin $E_2\;(PGE_2)$ assay was used to measure the COX-2 activity. Results: Ectopic expression of caveolin-1 induced COX-2 expression and activity, as indicated by immunoblot analysis and $PGE_2$ assay. And also, overexpression of caveolin-1 stimulated activation of p38 kinase and ERK-1/-2. Inhibition of p38 kinase and ERK-1/-2 with SB203580 and PD98059, respectively, led to a dose-dependent decrease COX-2 expression and $PGE_2$ production in caveolin-1-transfected cells. Conclusion: Taken together, our data suggest that ectopic expression of caveolin-1 contributes to the expression and activity of COX-2 in articular chondrocytes through MAP kinase pathway.

키워드

참고문헌

  1. Amin AR, Attur M, Abramson SB: Nitric oxide synthase and cyclooxygenases: distribution regulation and intervention in arthritis. Curr Opin Rheumatol 11;202-209, 1999 https://doi.org/10.1097/00002281-199905000-00009
  2. Smith W, Garavito R, DeWitt D: Prostaglandin endoperoxide H synthases (cyclooxygenases) -1 and -2. J Biol Chem 271; 33157-33160, 1996 https://doi.org/10.1074/jbc.271.52.33157
  3. Dubois RN, Abramson SB, Crofford L, Gupta RA, Somon LS, Van De Putte LB, Lipsky PE: Cyclooxygenase in biology and disease. FASEB J 12;1063-1073, 1998 https://doi.org/10.1096/fasebj.12.12.1063
  4. Wu KK: Inducible cyclooxygenase and nitric oxide synthase. Adv Pharmacol 33;179-207, 1995 https://doi.org/10.1016/S1054-3589(08)60669-9
  5. Lasa M, Mahtani KR, Finch A, Brewer G, Saklatvala J, Clark AR: Regulation of cyclooxygenase 2 mRNA stability by the mitogen-activated protein kinase p38 signaling cascade. Mol Cell Biol 20;4265-4274, 2000 https://doi.org/10.1128/MCB.20.12.4265-4274.2000
  6. Faour WH, He Y, He QW, de Ladurantaye M, Quintero M, Mancini A, Di Battista JA: Prostaglandin E2 regulates the level and stability of cyclooxygenase-2 mRNA through activation of p38 mitogen-activated protein kinase in interleukin-1 beta-treated human synovial fibroblasts. J Biol Chem 276; 31720-31731, 2001 https://doi.org/10.1074/jbc.M104036200
  7. Matsuura H, Sakaue M, Subbaramaiah K, Kamitani H, Eling TE, Dannenberg AJ, Tanabe T, Inoue H, Arata J, Jetten AM: Regulation of cyclooxygenase-2 by interferon gamma and transforming growth factor alpha in normal human epidermal keratinocytes and squamous carcinoma cells. Role of mitogen- activated protein kinases. J Biol Chem 274;29138-29148, 1999 https://doi.org/10.1074/jbc.274.41.29138
  8. Lisanti MP, Scherer P, Tang ZL, Sargiacomo M: Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis. Trends Cell Biol 4;231-235, 1994 9. Okamoto T, Scherer PE, Lisanti MP: Caveolins, a family of scaffolding proteins for organizing 'preassembled signaling complexes'at the plasma membrane. J Biol Chem 273; 5419-5422, 1998 https://doi.org/10.1074/jbc.273.10.5419
  9. Okamoto T, Scherer PE, Lisanti MP: Caveolins, a family of scaffolding proteins for organizing 'preassembled signaling complexes' at the plasma membrane. J Biol Chem 273; 5419-5422, 1998 https://doi.org/10.1074/jbc.273.10.5419
  10. Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG: Caveolin, a protein component of caveolae membrane coats. Cell 68;673-682, 1992 https://doi.org/10.1016/0092-8674(92)90143-Z
  11. Schwartz Z, Gilley RM, Sylvia VL, Dean DD, Boyan BD: The effect of prostaglandin E2 on costochondral chondrocyte differentiation is mediated by cyclic adenosine 3',5'- monophosphate and protein kinase C. Endocrinology 139; 1825-1834, 1998 https://doi.org/10.1210/en.139.4.1825
  12. Spencer AG, Woods JW, Arakawa T, Singer II, Smith WL: Subcellular localization of prostaglandin endoperoxide H synthases- 1 and -2 by immunoelectron microscopy. J Biol Chem 273;9886-9893, 1998 https://doi.org/10.1074/jbc.273.16.9886
  13. Liou JY, Shyue SK, Tsai MJ, Chung CL, Chu KY, Wu KK: Colocalization of prostacyclin synthase with prostaglandin H synthase-1 (PGHS-1) but not phorbol ester-induced PGHS-2 in cultured endothelial cells. J Biol Chem 275;15314-15320, 2000 https://doi.org/10.1074/jbc.275.20.15314
  14. Kim SJ, Ju JW, Oh CD, Yoon YM, Song WK, Kim JH, Yoo YJ, Bang OS, Kang SS, Chun JS: ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status. J Biol Chem 277;1332-1339, 2002 https://doi.org/10.1074/jbc.M107231200
  15. Kim SJ, Hwang SG, Shin DY, Kang SS, Chun JS: p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NF-kappa B-dependent transcription and stabilization by serine 15 phosphorylation. J Biol Chem 277;33501-33508, 2002 https://doi.org/10.1074/jbc.M202862200
  16. Yoon YM, Kim SJ, Oh CD, Ju JW, Song WK, Yoo YJ, Huh TL, Chun JS: Maintenance of differentiated phenotype of articular chondrocytes by protein kinase C and extracellular signal-regulated protein kinase. J Biol Chem 277; 8412-8420, 2002 https://doi.org/10.1074/jbc.M110608200
  17. Sargiacomo M, Sudol M, Tang ZL, Lisanti MP: Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J Cell Biol 122;789-807, 1993 https://doi.org/10.1083/jcb.122.4.789
  18. Lisanti MP, Scherer PE, Vidugiriene J, Tang ZL, Hermanoskivosatka A, Tu YH, Cook RF, Sargiacomo M: Characterization of caveolin-rich membrane domains isolated from an endothelial- rich source: implications for human disease. J Cell Biol 126;111-126, 1994 https://doi.org/10.1083/jcb.126.1.111
  19. Sandell LJ, Aigner I: Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 3;107-113, 2001 https://doi.org/10.1186/ar148
  20. Amin AR, Abramson SB: The role of nitric oxide in articular cartilage breakdown in osteoarthritis. Curr Opin Rheumatol 10;263-268, 1998 https://doi.org/10.1097/00002281-199805000-00018
  21. Kim SJ, Hwang SG, Kim IC, Chun JS: Actin cytoskelatal architecture regulates nitric oxide-induced apoptosis, dedifferentiation, and cyclooxygenase-2 expression in articular chondrocytes via mitogen-activated protein kinase and protein kinase C pathways. J Biol Chem 278;42448-42456, 2003 https://doi.org/10.1074/jbc.M304887200
  22. Hsieh HL, Wu CB, Sun CC, Liao CH, Lau YT, Yang CM: Sphingosine-1 phosphate induces COX-2 expression via PI3K/AKT and p42/44 MAPK pathways in rat vascular smooth muscle cells. J Cell Physiol 207;757-766, 2006 https://doi.org/10.1002/jcp.20621
  23. Nieminen R, Lahti A, Jalonen U, Kankaanranta H, Moilanen E: JNK inhibitor SP600125 reduces COX-2 expression by attenuating mRNA in activated murine J774 Macrophages. Int Immunopharmacol 6;987-996, 2006 https://doi.org/10.1016/j.intimp.2006.01.009
  24. Goldring MB, Berenbaum F: Human chondrocyte culture models for studying cyclooxygenase expression and prostaglandin regulation of collagen gene expression. Osteoarthritis Cartilage 7;386-388, 1999 https://doi.org/10.1053/joca.1998.0219
  25. Goldring MB, Suen LF, Yamin R, Lai WF: Regulation of collagen gene expression by prostaglandins and interleukin- 1beta in cultured chondrocytes and fibroblasts. Am J Ther 3;9-16, 1996 https://doi.org/10.1097/00045391-199601000-00003