Abstract
We previously showed that prostaglandin E2 (PGE2) stimulates multiple intracellular signaling pathways as follows: by activation of adenylate cyclase; phosphoinositide (PI)-hydrolyzing phospholipase C and phosphatidylcholine (PC)-hydrolyzing phospholipase D; and by induction of Ca2+ influx in osteoblast-like MC3T3-E1 cells. In this study, we investigated the effect of PGE2 on the synthesis of interleukin-6 (IL-6) and its regulatory mechanism in MC3T3-E1 cells. PGE2 significantly stimulated IL-6 secretion in a dose-dependent manner in the range between 1 nmol/L and 10 μmol/L. A23187, a calcium ionophore, or dibutyrgl-cAMP significantly induced IL-6 secretion. The effect of a combination of A23187 and dihutyryl-cAMP on IL-6 secretion was additive. The depletion of extracellular Ca2+ by EGTA reduced the PGE2-induced IL-6 secretion. EP1 receptor antagonist inhibited the PGE2-induced IL-6 secretion. H-89, an inhibitor of cAMP-dependent protein kinase, decreased the PGE2-induced IL-6 secretion. EP2 receptor agonist alone stimulated IL-6 secretion. However, EP4 receptor antagonist had little effect on IL-6 secretion. Calphostin C, a specific inhibitor of protein kinase C (PKC), enhanced the secretion of IL-6 induced by PGE2. The stimulative effect of PGE2 on IL-6 secretion was significantly enhanced in PKC downregulated MC3T3-E1 cells. Pertussis toxin enhanced PGE2-induced IL-6 secretion. These results strongly suggest that PGE2 stimulates IL-6 synthesis through both Ca2+ mobilization from extracellular space via EP1 receptor and cAMP production via EP2 receptor in osteoblast-like cells, and that the PKC activation by PGE2 itself regulates oversynthesis of IL-6.
| Original language | English |
|---|---|
| Pages (from-to) | 355-360 |
| Number of pages | 6 |
| Journal | Bone |
| Volume | 22 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 01-04-1998 |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Physiology
- Histology
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Interleukin-6 synthesis induced by prostaglandin E2 : Cross-talk regulation by protein kinase C. / Kozawa, O.; Suzuki, Atsushi; Tokuda, H.; Kaida, T.; Uematsu, T.
In: Bone, Vol. 22, No. 4, 01.04.1998, p. 355-360.Research output: Contribution to journal › Article
TY - JOUR
T1 - Interleukin-6 synthesis induced by prostaglandin E2
T2 - Cross-talk regulation by protein kinase C
AU - Kozawa, O.
AU - Suzuki, Atsushi
AU - Tokuda, H.
AU - Kaida, T.
AU - Uematsu, T.
PY - 1998/4/1
Y1 - 1998/4/1
N2 - We previously showed that prostaglandin E2 (PGE2) stimulates multiple intracellular signaling pathways as follows: by activation of adenylate cyclase; phosphoinositide (PI)-hydrolyzing phospholipase C and phosphatidylcholine (PC)-hydrolyzing phospholipase D; and by induction of Ca2+ influx in osteoblast-like MC3T3-E1 cells. In this study, we investigated the effect of PGE2 on the synthesis of interleukin-6 (IL-6) and its regulatory mechanism in MC3T3-E1 cells. PGE2 significantly stimulated IL-6 secretion in a dose-dependent manner in the range between 1 nmol/L and 10 μmol/L. A23187, a calcium ionophore, or dibutyrgl-cAMP significantly induced IL-6 secretion. The effect of a combination of A23187 and dihutyryl-cAMP on IL-6 secretion was additive. The depletion of extracellular Ca2+ by EGTA reduced the PGE2-induced IL-6 secretion. EP1 receptor antagonist inhibited the PGE2-induced IL-6 secretion. H-89, an inhibitor of cAMP-dependent protein kinase, decreased the PGE2-induced IL-6 secretion. EP2 receptor agonist alone stimulated IL-6 secretion. However, EP4 receptor antagonist had little effect on IL-6 secretion. Calphostin C, a specific inhibitor of protein kinase C (PKC), enhanced the secretion of IL-6 induced by PGE2. The stimulative effect of PGE2 on IL-6 secretion was significantly enhanced in PKC downregulated MC3T3-E1 cells. Pertussis toxin enhanced PGE2-induced IL-6 secretion. These results strongly suggest that PGE2 stimulates IL-6 synthesis through both Ca2+ mobilization from extracellular space via EP1 receptor and cAMP production via EP2 receptor in osteoblast-like cells, and that the PKC activation by PGE2 itself regulates oversynthesis of IL-6.
AB - We previously showed that prostaglandin E2 (PGE2) stimulates multiple intracellular signaling pathways as follows: by activation of adenylate cyclase; phosphoinositide (PI)-hydrolyzing phospholipase C and phosphatidylcholine (PC)-hydrolyzing phospholipase D; and by induction of Ca2+ influx in osteoblast-like MC3T3-E1 cells. In this study, we investigated the effect of PGE2 on the synthesis of interleukin-6 (IL-6) and its regulatory mechanism in MC3T3-E1 cells. PGE2 significantly stimulated IL-6 secretion in a dose-dependent manner in the range between 1 nmol/L and 10 μmol/L. A23187, a calcium ionophore, or dibutyrgl-cAMP significantly induced IL-6 secretion. The effect of a combination of A23187 and dihutyryl-cAMP on IL-6 secretion was additive. The depletion of extracellular Ca2+ by EGTA reduced the PGE2-induced IL-6 secretion. EP1 receptor antagonist inhibited the PGE2-induced IL-6 secretion. H-89, an inhibitor of cAMP-dependent protein kinase, decreased the PGE2-induced IL-6 secretion. EP2 receptor agonist alone stimulated IL-6 secretion. However, EP4 receptor antagonist had little effect on IL-6 secretion. Calphostin C, a specific inhibitor of protein kinase C (PKC), enhanced the secretion of IL-6 induced by PGE2. The stimulative effect of PGE2 on IL-6 secretion was significantly enhanced in PKC downregulated MC3T3-E1 cells. Pertussis toxin enhanced PGE2-induced IL-6 secretion. These results strongly suggest that PGE2 stimulates IL-6 synthesis through both Ca2+ mobilization from extracellular space via EP1 receptor and cAMP production via EP2 receptor in osteoblast-like cells, and that the PKC activation by PGE2 itself regulates oversynthesis of IL-6.
UR - http://www.scopus.com/inward/record.url?scp=17444443612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17444443612&partnerID=8YFLogxK
U2 - 10.1016/S8756-3282(97)00293-7
DO - 10.1016/S8756-3282(97)00293-7
M3 - Article
C2 - 9556135
AN - SCOPUS:17444443612
VL - 22
SP - 355
EP - 360
JO - Bone
JF - Bone
SN - 8756-3282
IS - 4
ER -