TY - JOUR
T1 - Protein kinase C activation by interleukin (IL)-1 limits IL-1-induced IL-6 synthesis in osteoblast-like cells
T2 - Involvement of phosphatidylcholine- specific phospholipase C
AU - Kozawa, Osamu
AU - Suzuki, Atsushi
AU - Tokuda, Haruhiko
AU - Kaida, Takehiro
AU - Uematsu, Toshihiko
PY - 1997/10/1
Y1 - 1997/10/1
N2 - We investigated the regulatory mechanism of interleukin-6 (IL-6) synthesis induced by interleukin-1 (IL-1) in osteoblast-like MC3T3-E1 cells. IL-1 stimulated the secretion of IL-6 in a dose-dependent manner in the range between 0.1 and 100 ng/ml. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), significantly enhanced the IL-1-induced secretion of IL-6. The stimulative effect of IL-1 was markedly amplified in PKC down- regulated MC3T3-E1 cells. IL-1 produced diacylglycerol in MC3T3-E1 cells. IL- 1 had little effect on the formation of inositol phosphates and choline. On the contrary, IL-1 significantly stimulated the formation of phosphocholine dose-dependently. D-609, an inhibitor of phosphatidylcholine-specific phospholipase C, suppressed the IL-1-induced diacylglycerol production. The IL-1 -induced IL-6 secretion was significantly enhanced by D-609. These results indicate that IL-1 activates PKC via phosphatidylcholine-specific phospholipase C in osteoblast-like cells, and the PKC activation then limits IL-6 synthesis induced by IL-1 itself.
AB - We investigated the regulatory mechanism of interleukin-6 (IL-6) synthesis induced by interleukin-1 (IL-1) in osteoblast-like MC3T3-E1 cells. IL-1 stimulated the secretion of IL-6 in a dose-dependent manner in the range between 0.1 and 100 ng/ml. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), significantly enhanced the IL-1-induced secretion of IL-6. The stimulative effect of IL-1 was markedly amplified in PKC down- regulated MC3T3-E1 cells. IL-1 produced diacylglycerol in MC3T3-E1 cells. IL- 1 had little effect on the formation of inositol phosphates and choline. On the contrary, IL-1 significantly stimulated the formation of phosphocholine dose-dependently. D-609, an inhibitor of phosphatidylcholine-specific phospholipase C, suppressed the IL-1-induced diacylglycerol production. The IL-1 -induced IL-6 secretion was significantly enhanced by D-609. These results indicate that IL-1 activates PKC via phosphatidylcholine-specific phospholipase C in osteoblast-like cells, and the PKC activation then limits IL-6 synthesis induced by IL-1 itself.
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U2 - 10.1002/(SICI)1097-4644(19971001)67:1<103::AID-JCB11>3.0.CO;2-I
DO - 10.1002/(SICI)1097-4644(19971001)67:1<103::AID-JCB11>3.0.CO;2-I
M3 - Article
C2 - 9328844
AN - SCOPUS:0030984057
SN - 0730-2312
VL - 67
SP - 103
EP - 111
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 1
ER -