scholarly journals (-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Shinji Takai ◽  
Rie Matsushima-Nishiwaki ◽  
Seiji Adachi ◽  
Hideo Natsume ◽  
Chiho Minamitani ◽  
...  
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Interleukin 6 ◽  
Epigallocatechin Gallate ◽  
P38 Map Kinase ◽  
Platelet Derived Growth Factor ◽  
S6 Kinase ◽  
Jnk Pathway ◽  
P70 S6 Kinase ◽  
Mitogen Activated Protein

We previously showed that the mitogen-activated protein (MAP) kinase superfamily, p44/p42 MAP kinase, p38 MAP kinase, and stress-activated protein kinase (SAPK)/c-JunN-terminal (JNK), positively plays a part in the platelet-derived growth factor-BB- (PDGF-BB-) stimulated synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells while Akt and p70 S6 kinase negatively regulates the synthesis. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, affects the synthesis of IL-6 in these cells and the mechanism. EGCG significantly reduced the IL-6 synthesis and IL-6 mRNA expression stimulated by PDGF-BB, EGCG reduced the PDGF-BB-stimulated IL-6 synthesis also in primary-cultured osteoblasts. EGCG had no effect on the levels of osteocalcin and osteoprotegerin in MC3T3-E1 cells. The PDGF-BB-induced autophosphorylation of PDGF receptorβwas not suppressed by EGCG. The PDGF-BB-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was not affected by EGCG. On the other hand, EGCG markedly suppressed the PDGF-BB-induced phosphorylation of SAPK/JNK. Finally, the PDGF-BB-induced phosphorylation of Akt and p70 S6 kinase was not affected by EGCG. These results strongly suggest that EGCG inhibits the PDGF-BB-stimulated synthesis of IL-6 via suppression of SAPK/JNK pathway in osteoblasts.

scholarly journals HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Gen Kuroyanagi ◽  
Go Sakai ◽  
Takanobu Otsuka ◽  
Naohiro Yamamoto ◽  
Kazuhiko Fujita ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Map Kinase ◽  
Interleukin 6 ◽  
Prostaglandin F2α ◽  
P38 Map Kinase ◽  
Vascular Endothelial ◽  
Mitogen Activated Protein ◽  
Endothelial Growth Factor ◽  
Vegf Release

Abstract Background Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells. Methods MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation. Conclusions Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

scholarly journals HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts

2020 ◽  
Author(s):  
Gen Kuroyanagi ◽  
Go Sakai ◽  
Takanobu Otsuka ◽  
Naohiro Yamamoto ◽  
Kazuhiko Fujita ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Map Kinase ◽  
Interleukin 6 ◽  
Prostaglandin F2α ◽  
P38 Map Kinase ◽  
Vascular Endothelial ◽  
Mitogen Activated Protein ◽  
Endothelial Growth Factor ◽  
Vegf Release

Abstract Background: Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitously expression including in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF, and the mechanism in MC3T3-E1 cells. Methods: MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results: The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 down-regulation. Conclusions: Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

scholarly journals HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts

2020 ◽  
Author(s):  
Gen Kuroyanagi ◽  
Go Sakai ◽  
Takanobu Otsuka ◽  
Naohiro Yamamoto ◽  
Kazuhiko Fujita ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Map Kinase ◽  
Interleukin 6 ◽  
Prostaglandin F2α ◽  
P38 Map Kinase ◽  
Vascular Endothelial ◽  
Mitogen Activated Protein ◽  
Endothelial Growth Factor ◽  
Vegf Release

Abstract Background: Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitously expression including in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF, and the mechanism in MC3T3-E1 cells. Methods: MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results: The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 down-regulation. Conclusions: Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

p38 MAP kinase negatively regulates cyclin D1 expression in airway smooth muscle cells

2001 ◽  
Vol 280 (5) ◽  
pp. L955-L964 ◽  
Author(s):  
Kristen Page ◽  
Jing Li ◽  
Marc B. Hershenson
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Cyclin D1 ◽  
Growth Regulation ◽  
P38 Map Kinase ◽  
Dominant Negative ◽  
Platelet Derived Growth Factor ◽  
Airway Smooth Muscle Cells ◽  
Erk Activation ◽  
Erk Phosphorylation

We have demonstrated that platelet-derived growth factor (PDGF) stimulates p38 mitogen-activated protein (MAP) kinase activation in bovine tracheal myocytes, suggesting that p38 is involved in growth regulation. We therefore examined whether p38 regulates expression of cyclin D1, a G1 cyclin required for cell cycle traversal. The chemical p38 inhibitors SB-202190 and SB-203580 each increased basal and PDGF-induced cyclin D1 promoter activity and protein abundance. Overexpression of a dominant negative allele of MAP kinase kinase-3 (MKK3), an upstream activator of p38α, had similar effects. Conversely, active MKK3 and MKK6, both of which increase p38α activity, each decreased transcription from the cyclin D1 promoter. Together, these data demonstrate that p38 negatively regulates cyclin D1 expression. We tested whether p38 regulates cyclin D1 expression via inhibition of extracellular signal-regulated kinase (ERK) activation. Chemical inhibitors of p38 induced modest ERK phosphorylation and activation. However, dominant negative MKK3 was insufficient to activate ERK, and active MKK3 and MKK6 did not attenuate platelet-derived growth factor-mediated ERK activation. These data are consistent with the notion that p38α negatively regulates cyclin D1 expression via an ERK-independent pathway.

scholarly journals Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration

2009 ◽  
Vol 202 (2) ◽  
pp. 309-316 ◽  
Author(s):  
Keisuke Ishizawa ◽  
Narantungalag Dorjsuren ◽  
Yuki Izawa-Ishizawa ◽  
Rika Sugimoto ◽  
Yasumasa Ikeda ◽  
...  
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Map Kinase ◽  
Intracellular Signaling ◽  
Mesangial Cell ◽  
Kinase Inhibitor ◽  
P38 Map Kinase ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner ◽  
Plasma Adiponectin

Adiponectin, an adipocyte-derived hormone, has been involved in metabolic syndrome, a known risk factor for the development of chronic kidney disease (CKD). Recent studies have demonstrated that plasma adiponectin levels are elevated when kidney function declines in patients with CKD. Excessive mesangial cell (MC) turnover is one of the important features of CKD. The aim of the present study is to elucidate the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell migration and intracellular signaling pathways, in cultured rat MCs (RMCs). PDGF-induced RMC migration was significantly inhibited by the pretreatment of adiponectin. Adiponectin alone had no effect on RMC migration. Big mitogen-activated protein (MAP) kinase 1 (BMK1), p38 MAP kinase, and Akt were activated by PDGF stimulation in a time- and concentration-dependent manner in RMC. Adiponectin alone did not affect BMK1, p38 MAP kinase, and Akt phosphorylations in RMC. PDGF-induced BMK1 and p38 MAP kinase phosphorylations were significantly attenuated by the pretreatment of adiponectin in RMCs. On the other hand, the phosphorylation of Akt by PDGF was not diminished by the pretreatment of adiponectin. Adiponectin had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that PDGF-induced RMC migration was significantly suppressed by siBMK1 transfection or SB203580, a p38 MAP kinase inhibitor. From these findings, it is implied that the elevated plasma adiponectin levels in patients with CKD might play a compensatory role aimed at counteracting renal dysfunction related to MC disorders.

p38 MAP kinase mediates platelet-derived growth factor-stimulated migration of hepatic myofibroblasts

2002 ◽  
Vol 191 (3) ◽  
pp. 351-361 ◽  
Author(s):  
Pisit Tangkijvanich ◽  
Chintda Santiskulvong ◽  
Andrew C. Melton ◽  
Enrique Rozengurt ◽  
Hal F. Yee,
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Platelet Derived Growth Factor
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