Compounds > inositol-1-4-5-trisphosphate

inositol-1-4-5-trisphosphate and Osteoarthritis

inositol-1-4-5-trisphosphate has been researched along with Osteoarthritis* in 1 studies

Other Studies

1 other study(ies) available for inositol-1-4-5-trisphosphate and Osteoarthritis

Article	Year
Signal transduction of beta2m-induced expression of VCAM-1 and COX-2 in synovial fibroblasts. Kidney international, 2002, Volume: 61, Issue:2 beta2 microglobulin (beta2m) amyloidosis is a destructive articular disease affecting dialysis patients. We have demonstrated that beta2m increases the expression of vascular cell adhesion molecule (VCAM-1) and cyclooxygenase-2 (COX-2) in human osteoarthritic synovial fibroblasts (SFLs).. To determine the cell signaling pathways, SFLs were incubated with beta2m in the presence or absence of various inhibitors for 24 hours. Intracellular calcium ([Ca2+]i) was measured by fluorometric techniques and vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2) expression was determined by immunohistochemistry and Western blotting.. beta2m increased [Ca2+]i levels in a dose dependent manner (P < 0.05) in SFLs. BAPTA-AM, a [Ca2+]i chelator, completely inhibited beta2m-induced expression of VCAM-1 and COX-2. U73122 [phospholipase C (PLC) inhibitor] or 2-APB [specific inhibitor of inositol 1,4,5-trisphosphate (IP3)-induced [Ca2+]i release] completely blocked the beta2m-induced increase in [Ca2+]i and the up-regulation of VCAM-1 and COX-2. However, pretreatment with staurosporin, a protein kinase C inhibitor, had no effect. Disruption of the actin cytoskeleton by treatment with cytochalasin D or latrunculin A blocked beta2m up-regulation of VCAM-1 and COX-2. Finally, cells treated with phosphatidylinositol-3 kinase (PI-3 kinase) inhibitors wortmannin or LY294002 also failed to express VCAM-1 and COX-2.. These results demonstrate that IP3-mediated [Ca2+]i release, PI-3 kinase, and actin cytoskeleton reorganization are involved in beta2m-induced expression of VCAM-1 and COX-2 in human SFLs. Understanding the potential pathways by which beta2m exerts its inflammatory-like effects may lead to the development of future therapies. Topics: Actins; Amyloidosis; beta 2-Microglobulin; Calcium; Calcium Signaling; Cells, Cultured; Cyclooxygenase 2; Cytoskeleton; Enzyme Inhibitors; Fibroblasts; Humans; Inositol 1,4,5-Trisphosphate; Isoenzymes; Kidney Failure, Chronic; Membrane Proteins; Osteoarthritis; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Prostaglandin-Endoperoxide Synthases; Synovial Membrane; Vascular Cell Adhesion Molecule-1	2002

Article

Year

Signal transduction of beta2m-induced expression of VCAM-1 and COX-2 in synovial fibroblasts.

Kidney international, 2002, Volume: 61, Issue:2

beta2 microglobulin (beta2m) amyloidosis is a destructive articular disease affecting dialysis patients. We have demonstrated that beta2m increases the expression of vascular cell adhesion molecule (VCAM-1) and cyclooxygenase-2 (COX-2) in human osteoarthritic synovial fibroblasts (SFLs).. To determine the cell signaling pathways, SFLs were incubated with beta2m in the presence or absence of various inhibitors for 24 hours. Intracellular calcium ([Ca2+]i) was measured by fluorometric techniques and vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2) expression was determined by immunohistochemistry and Western blotting.. beta2m increased [Ca2+]i levels in a dose dependent manner (P < 0.05) in SFLs. BAPTA-AM, a [Ca2+]i chelator, completely inhibited beta2m-induced expression of VCAM-1 and COX-2. U73122 [phospholipase C (PLC) inhibitor] or 2-APB [specific inhibitor of inositol 1,4,5-trisphosphate (IP3)-induced [Ca2+]i release] completely blocked the beta2m-induced increase in [Ca2+]i and the up-regulation of VCAM-1 and COX-2. However, pretreatment with staurosporin, a protein kinase C inhibitor, had no effect. Disruption of the actin cytoskeleton by treatment with cytochalasin D or latrunculin A blocked beta2m up-regulation of VCAM-1 and COX-2. Finally, cells treated with phosphatidylinositol-3 kinase (PI-3 kinase) inhibitors wortmannin or LY294002 also failed to express VCAM-1 and COX-2.. These results demonstrate that IP3-mediated [Ca2+]i release, PI-3 kinase, and actin cytoskeleton reorganization are involved in beta2m-induced expression of VCAM-1 and COX-2 in human SFLs. Understanding the potential pathways by which beta2m exerts its inflammatory-like effects may lead to the development of future therapies.

Topics: Actins; Amyloidosis; beta 2-Microglobulin; Calcium; Calcium Signaling; Cells, Cultured; Cyclooxygenase 2; Cytoskeleton; Enzyme Inhibitors; Fibroblasts; Humans; Inositol 1,4,5-Trisphosphate; Isoenzymes; Kidney Failure, Chronic; Membrane Proteins; Osteoarthritis; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Prostaglandin-Endoperoxide Synthases; Synovial Membrane; Vascular Cell Adhesion Molecule-1

2002