TY - JOUR
T1 - Ca2+ stimulates COX-2 expression through calcium-sensing receptor in fibroblasts
AU - Ogata, Sachie
AU - Kubota, Yasutaka
AU - Satoh, Shinji
AU - Ito, Shinich
AU - Takeuchi, Hiroshi
AU - Ashizuka, Megumi
AU - Shirasuna, Kanemitsu
N1 - Funding Information:
This work was supported by a Grant-in-Aid from the Ministry of Education of Japan (No. 18592188).
PY - 2006/12/29
Y1 - 2006/12/29
N2 - Fibroblasts isolated from jaw cysts expressed calcium-sensing receptor (CasR). In the fibroblasts elevated extracellular Ca2+ ([Ca2+]o) increased fluo-3 fluorescence intensity, and the production of inositol(1,4,5)trisphosphate and active protein kinase C. Phospholipase C inhibitor U-73122 attenuated the Ca2+-induced increase in fluo-3 fluorescence intensity. Elevated [Ca2+]o enhanced the expression of cyclooxygenase-2 (COX-2) mRNA and protein, and the secretion of prostaglandin E2 in the fibroblasts. CasR activator neomycin also increased the expression of COX-2 mRNA, and U-73122 attenuated the Ca2+-induced expression of COX-2 mRNA. Elevated [Ca2+]o-induced phosphorylation of extracellular signal-regulated protein kinase-1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK), and U-73122 inhibited the Ca2+-induced phosphorylation. The inhibitors for each kinase, PD98059, SB203580, and SP600125, attenuated the Ca2+-induced expression of COX-2 mRNA. These results suggest that in jaw cyst fibroblasts elevated extracellular Ca2+ may enhance COX-2 expression via the activation of ERK1/2, p38 MAPK, and JNK through CasR.
AB - Fibroblasts isolated from jaw cysts expressed calcium-sensing receptor (CasR). In the fibroblasts elevated extracellular Ca2+ ([Ca2+]o) increased fluo-3 fluorescence intensity, and the production of inositol(1,4,5)trisphosphate and active protein kinase C. Phospholipase C inhibitor U-73122 attenuated the Ca2+-induced increase in fluo-3 fluorescence intensity. Elevated [Ca2+]o enhanced the expression of cyclooxygenase-2 (COX-2) mRNA and protein, and the secretion of prostaglandin E2 in the fibroblasts. CasR activator neomycin also increased the expression of COX-2 mRNA, and U-73122 attenuated the Ca2+-induced expression of COX-2 mRNA. Elevated [Ca2+]o-induced phosphorylation of extracellular signal-regulated protein kinase-1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK), and U-73122 inhibited the Ca2+-induced phosphorylation. The inhibitors for each kinase, PD98059, SB203580, and SP600125, attenuated the Ca2+-induced expression of COX-2 mRNA. These results suggest that in jaw cyst fibroblasts elevated extracellular Ca2+ may enhance COX-2 expression via the activation of ERK1/2, p38 MAPK, and JNK through CasR.
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U2 - 10.1016/j.bbrc.2006.10.098
DO - 10.1016/j.bbrc.2006.10.098
M3 - Article
C2 - 17097611
AN - SCOPUS:33750817113
SN - 0006-291X
VL - 351
SP - 808
EP - 814
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -