Involvement of Protein Kinase C Activation in Endothelin-1-induced Secretion of Interleukin-6 in Osteoblast-like Cells

Matsuno, Mitsuhiro; Kozawa, Osamu; Suzuki, Atsushi; Tokuda, Harukuni; Kaida, Takehiro; Matsuno, Hiroyuki; Niwa, Masayuki

doi:10.1016/s0898-6568(97)00113-7

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…An intimate functional relationship exists between bone vascular endothelium and osteoblastic cells during osteogenesis, in which complex hormones and growth factors mediate signals and play an active role [Guenther et al, 1986;Villanueva et al, 1990;Collin-Osdoby et al, 1994;Decker et al, 1995, Formigli et al, 1997Matusuno et al, 1998]. Angiogenesis is induced by a variety of growth factors, but vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), appears to be a unique potent endothelial cell-specific cytokine, inducing both vascular permeability and angiogenesis in vivo [Dvorak et al, 1995;Ferrara et al, 1997].…”

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confidence: 99%

Effect of human endothelial cells on Human Bone Marrow Stromal Cell phenotype: Role of VEGF?

et al. 2000

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Angiogenesis is a tightly regulated process involved in growth, repair, and bone remodeling. Several studies have shown that there is a reciprocal regulation and functional relationship between endothelial cells and osteoblast-like cells during osteogenesis, where systemic hormones and paracrine growth factors play an active role. Angiogenesis is induced by a variety of growth factors; among them vascular endothelial growth factor (VEGF) may be an important mediator for the angiogenic process involved in bone physiology. We studied the VEGF effect on osteoblast progenitor cells (Human Bone Marrow Stromal Cells: HBMSE) cultured alone or associated with endothelial cells (Human Umbilical Vein Endothelial Cells: HUVEC) in different co-culture models (co-culture with or without direct contact, conditioned medium), to determine the influence of VEGF on these cells and on their relationship. In agreement with other studies, we show that HBMSC express and synthesize VEGF, HUVEC conditioned medium has a proliferative effect on them, and early osteoblastic marker (Alkaline phosphatase activity) levels increase when these cells are co-cultured with HUVEC only in direct contact. However, unlike previous studies, we did not find that VEGF increased these processes. These results suggest that the intercommunication between endothelial cells and osteoblastic-like cells requires not only diffusible factors, but also involving cell membrane proteins.

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confidence: 99%

Effect of human endothelial cells on Human Bone Marrow Stromal Cell phenotype: Role of VEGF?

et al. 2000

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“…Until now, little is known about PKC dependence of IL-6 biosynthesis in macrophages, although PKC seems to be involved in IL-6 production in human fibroblast [1,35,40], bone marrow stroma [34], lymphocytes [15], epidermoid carcinoma cells [13], vascular smooth muscle cells [3], myoblast [8] and osteoblast [29]. The role of PKC activation in monocytes/macrophages is still a matter of controversy.…”

Section: Discussionmentioning

confidence: 99%

Potentiation of Lipopolysaccharide-Induced IL-6 Release by Uridine Triphosphate in Macrophages: Cross-Interaction with Cyclooxygenase-2-Dependent Prostaglandin E<sub>2</sub> Production

Chen

Lin²

1999

J Biomed Sci

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Our previous study has demonstrated the potentiation by uridine triphosphate (UTP) of nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in lipopolysaccharide (LPS)-stimulated murine J774 macrophages. In this study, we found that the amount of interleukin-6 (IL-6) release in response to LPS stimulation was greatly enhanced in the presence of UTP. This enhancement exhibited concentration dependence and occurred after 8 h of treatment with LPS. RT-PCR analysis indicated that the steady-state level of IL-6 mRNA induced by LPS was apparently increased upon co-addition of UTP. The potentiation by UTP was inhibited by the treatment with U73122 (a phosphatidylinositol-phospholipase C inhibitor), BAPTA/AM (an intracellular Ca²⁺ chelator), KN-93 (a selective inhibitor of calmodulin-dependent protein kinase) or PDTC (a nuclear factor κB inhibitor). To understand the cross-regulation among NO, PGE₂ and IL-6, all of which are dramatically induced after LPS stimulation, the effects of L-NAME (a nitric oxide synthase inhibitor), indomethacin (a cyclooxygenase inhibitor), NS-398 (a cycloxygenase-2 inhibitor) and IL-6 antibody were tested. The results revealed the positive regulation between PGE₂ and IL-6 synthesis because NS-398 and indomethacin inhibited LPS plus UTP-induced IL-6 release, and IL-6 antibody attenuated LPS plus UTP-induced PGE₂ release. Taken together these results reinforce the role of UTP as a regulatory element in inflamed sites by demonstrating the capacity of this nucleotide to potentiate LPS-induced release of inflammatory mediators.

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“…We have recently reported that PKC positively or negatively regulates IL-6 synthesis depending upon the intracellular signaling systems of each agonists in osteoblast-like MC3T3-E1 cells [Kozawa et al, 1997a[Kozawa et al, -e, 1998aMatsuno et al, 1998]. To investigate the role of PKC in the regulation of sphingomyelinaseinduced IL-6 synthesis, the effect of calphostin C, a highly potent and specific inhibitor of PKC [Kobayashi et al, 1989], was examined.…”

Section: Effect Of Calphostin C On Sphingomyelinase-induced Il-6 Syntmentioning

confidence: 99%

“…It has been reported that the receptors of endothelin, produced by endothelial cells [Masaki, 1993;Pollock et al, 1995], exist on cultured osteoblasts [Takuwa et al, 1989;Sakurai et al, 1992;Semler et al, 1995], and that endothelin-1 modulates cell functions of osteoblasts through activating intracellular signaling systems such as phospholipase C and Ca 2ϩ mobilization [Takuwa et al, 1989;Tatrai et al, 1992a,b], suggesting the intercellular communications between endothelial cells and osteoblasts via secretion of bioactive substances. We have recently reported that endothelin-1 induces interleukin-6 (IL-6) synthesis in osteoblast-like MC3T3-E1 cells [Matsuno et al, 1998]. However, the intercellular signaling mechanism among endothelial cells, osteoblasts, and osteoclasts has not yet been fully clarified.…”

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confidence: 99%

“…As for the regulation of IL-6 synthesis by osteoblasts, it has been reported that PDGF stimulates IL-6 synthesis through the activation of protein kinase C (PKC) in primary cultured osteoblasts [Franchimont and Canalis, 1995]. We have recently reported that PKC activation mediates the stimulatory effects of prostaglandin F 2␣ or endothelin-1 on IL-6 synthesis in osteoblastlike MC3T3-E1 cells [Kozawa et al, 1997a;Matsuno et al, 1998]. On the contrary, we have shown that the IL-6 synthesis induced by basic fibroblast growth factor, prostaglandin E 2 , thrombin, IL-1, or TNF is negatively regulated by PKC in these cells [Kozawa et al, 1997b[Kozawa et al, -e, 1998a.…”

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confidence: 99%

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Extracellular sphingomyelinase induces interleukin-6 synthesis in osteoblasts

1999

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In osteoblast-like MC3T3-E1 cells, we have recently reported that sphingosine 1-phosphate among sphingomyelin metabolites acts as a second messenger for tumor necrosis factor-alpha (TNF)-induced interleukin-6 (IL-6) synthesis. In the present study, we investigated the effect of extracellular sphingomyelinase on IL-6 synthesis in MC3T3-E1 cells. Sphingomyelinase stimulated IL-6 synthesis in a time-dependent manner for up to 24 h. This stimulative effect was dose dependent in the range between 1 and 300 mU/ml. Calphostin C, a highly and potent inhibitor of protein kinase C, enhanced sphingomyelinase-induced IL-6 synthesis. DL-Threo-dihydrosphingosine, an inhibitor of sphingosine kinase, significantly inhibited the IL-6 synthesis induced by sphingomyelinase. Sphingomyelinase markedly elicited sphingomyelin hydrolysis. In addition, the effect of a combination of sphingomyelinase and TNF on IL-6 synthesis was synergistic. These results strongly suggest that extracellular sphingomyelinase induces sphingomyelin hydrolysis in osteoblasts, resulting in IL-6 synthesis, and that protein kinase C acts as a negative controller of the IL-6 synthesis.

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Involvement of Protein Kinase C Activation in Endothelin-1-induced Secretion of Interleukin-6 in Osteoblast-like Cells

Cited by 17 publications

References 29 publications

Effect of human endothelial cells on Human Bone Marrow Stromal Cell phenotype: Role of VEGF?

Effect of human endothelial cells on Human Bone Marrow Stromal Cell phenotype: Role of VEGF?

Potentiation of Lipopolysaccharide-Induced IL-6 Release by Uridine Triphosphate in Macrophages: Cross-Interaction with Cyclooxygenase-2-Dependent Prostaglandin E<sub>2</sub> Production

Extracellular sphingomyelinase induces interleukin-6 synthesis in osteoblasts

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