• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.199-210
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• 2003

Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.148.1-148.1
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• 2003

Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. Previously, we have shown that ceramide induces Bax translocation which is associated with cytochrome c release from the mitochondria. In this study, we show that p38 MAP kinase is involved in ceramide-induced Bax translocation. In human leukemic cells, ceramide stimulated the phosphorylation of p38 MAP kinase. Preincubation of cells with SB203580, a specific inhibitor of p38 inhibited DNA fragmentation induced by cell-permeable ceramide. (omitted)

• Biomedical Science Letters
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• v.15 no.2
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• pp.141-146
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• 2009

Paclitaxel, an antimicrotubule agent, binds to beta-tubulin in the microtubule and stabilizes the polymer, thereby repressing dynamic instability. Here, we have demonstrated that microtubule cytoskeletal architecture involved in regulation of the COX-2 expression in chondrocyte treated with paclitaxel. Paclitaxel enhanced COX-2 expression and prostaglandin E2 production, as indicated by the Western blot analysis, reverse transcriptase PCR(RT-PCR) and immunofluorescence staining, and $PGE_2$ assay, respectively. In our previous data have shown that paclitaxel treatment stimulated activation of ERK-1/2 and p38 kinase(Im et al., 2009). SB203580, an inhibitor of p38 kinase, blocked the induction of COX-2 expression by paclitaxel. Also PD98059, an inhibitor of ERK-1/2 kinase was blocked the induced COX-2 expression. These results indicate that activation of ERK-1/2 and p38 kinase is required for COX-2 expression induced by paclitaxel in rabbit articular chondrocytes.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• Applied Biological Chemistry
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• v.51 no.2
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• pp.129-135
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• 2008

Berberine is an isoquinoline alkaloid used in traditional Chinese medicine and has been isolated from a variety of plants, such as Coptis chinensis and Phellodendron amurense. It has a wide spectrum of clinical applications such as in anti-tumor, anti-microbial, and anti-inflammatory activities. However, it is still unknown that berberine related with reactive oxygen species (ROS)-mediated apoptosis pathway in human hepatoma HepG2 cells. In the present study, we are examined the molecular mechanism of ROS- and p38 MAP kinase-mediated apoptosis by berberine in HepG2 cells. Berberine increased cytotoxicity effects by time- and does-dependent manner. $LD_{50}$ was detected 50 ${\mu}M$ at 48h of exposure to berberine. Nuclei cleavage and apoptotic DNA fragmentation were observed in cells treated with 50 ${\mu}M$ of berberine for 48h. Moreover, berberine induced the activating of caspase-3, p53, p38 and Bax expression, whereas the expression of anti-apoptotic signaling pathways, Bcl-2, was decreased. Additionally, berberine-treated cells had an increased level of generation of ROS and nitric oxide (NO). These results indicated that berberine induces apoptosis of HepG2 cells may be mediated oxidative injury acts as an early and upstream change, triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, p38 and p53 activation, caspase-3 activation, and consequent leading to apoptosis.

• Toxicological Research
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• v.17
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• pp.251-256
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• 2001

The expression of phase II detoxifying enzymes is affected by a variety of compounds and the induction of the enzymes plays an essential role in chemoprevention. A variety of phytochemicals such as sulfur-containing chemoprotective agents (SCC) may trigger cellular signals and activate phase II gene expression through ARE activation. see induces glutathione S-transferases. Studies were conducted to investigate the role of mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3-kinase) in the induction of GST (e.g. rGSTA2) by sec. We also studied the MAP kinase pathway responsible for the GST expression by see and compared that with the pathway activated by oxidative stress as a result of sulfur amino acids deprivation (SAAD). see inhibited phosphorylation of ERK1/2 although the effect of see on JNK and p38 MAP kinase was minimal. Wortmannin and LY294002. PI3-kinase inhibitors. abolished the increases in rGSTA2 mRNA and protein levels by SCC. Deprivation of cystine and methionine caused oxidative stress in H4IIE cells. as evidenced by a decrease in the reduced glutathione and an increase in prooxidant production. Electrophoretic mobility shift assay revealed that the ARE complex consisting of Nrf-1/2 and Maf proteins was activated 12~48 h. The rGSTA2 mRNA and protein levels were increased by SAAD. Activation of ARE and induction of rGSTA2 were both completely inhibited by PI3-kinase inhibitors. Inhibition of p38 MAP kinase by SB203580 prevented the ARE-mediated rGSTA2 induction. The results of this study showed that PI3-kinase might play an essential role in the ARE-mediated rGSTA2 induction by see or SAAD and that the dual MAP kinase pathways were responsible for the enzyme induction.

• BMB Reports
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• v.57 no.5
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• pp.238-243
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• 2024

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into endothelial cells in an inflammatory microenvironment. However, the regulatory mechanisms underlying this process are not entirely understood. Here, we found that TIE2 in BM-MSCs was upregulated at the transcriptional level after stimulation with tumor necrosis factor-alpha (TNFα), a major pro-inflammatory cytokine. Additionally, the STAT-binding sequence within the proximal region of TIE2 was necessary for TNFα-induced TIE2 promoter activation. TIE2 and STAT3 knockdown reduced TNFα-induced endothelial tube formation in BM-MSCs. Among the major TNFα-activated MAP kinases (ERK1/2, JNK1/2, and p38 MAPK) in BM-MSCs, only inhibition of the p38 kinase abrogated TNFα-induced TIE2 upregulation by inhibiting the JAK-STAT signaling pathway. These findings suggest that p38 MAP contributes to the endothelial differentiation of BM-MSCs by activating the JAK-STAT-TIE2 signaling axis in the inflammatory microenvironment.

• Journal of Korean Neurosurgical Society
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• v.56 no.1
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• pp.1-4
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• 2014

Objective : The aims of our study are to evaluate the effect of curcumin on spinal cord neural progenitor cell (SC-NPC) proliferation and to clarify the mechanisms of mitogen-activated protein (MAP) kinase signaling pathways in SC-NPCs. Methods : We established cultures of SC-NPCs, extracted from the spinal cord of Sprague-Dawley rats weighing 250 g to 350 g. We measured proliferation rates of SC-NPCs after curcumin treatment at different dosage. The immuno-blotting method was used to evaluate the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs), p38, c-Jun $NH_2$-terminal kinases (JNKs) and ${\beta}$-actin as the control group. Results : Curcumin has a biphasic effect on SC-NPC proliferation. Lower dosage (0.1, 0.5, $1{\mu}M$) of curcumin increased SC-NPC proliferation. However, higher dosage decreased SC-NPC proliferation. Also, curcumin stimulates proliferation of SC-NPCs via the MAP kinase signaling pathway, especially involving the p-ERK and p-38 protein. The p-ERK protein and p38 protein levels varied depending on curcumin dosage (0.5 and $1{\mu}M$, p<0.05). Conclusion : Curcumin can stimulate proliferation of SC-NPCs via ERKs and the p38 signaling pathway in low concentrations.

• IMMUNE NETWORK
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• v.6 no.3
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• pp.123-127
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• 2006

Background: Caveolin-1 is a principal component of caveolae membranes in vivo. Although expression of caveolae structure and expression of caveolin family, caveolin-1, -2 and -3, was known in chondrocytes, the functional role of caveolae and caveolins in chondrocytes remains unknown. In this study, we investigated the role of caveolin-1 in articular chondrocytes. Methods: Rabbit articular chondrocytes were prepared from cartilage slices of 2-week-old New Zealand white rabbits by enzymatic digestion. Caveolin-1 cDNA was transfected to articular chondrocytes using LipofectaminePLUS. The cyclooxygenase-2 (COX-2) expression levels were determined by immunoblot analysis, immunostaining, immunohistochemistry, and prostaglandin $E_2\;(PGE_2)$ assay was used to measure the COX-2 activity. Results: Ectopic expression of caveolin-1 induced COX-2 expression and activity, as indicated by immunoblot analysis and $PGE_2$ assay. And also, overexpression of caveolin-1 stimulated activation of p38 kinase and ERK-1/-2. Inhibition of p38 kinase and ERK-1/-2 with SB203580 and PD98059, respectively, led to a dose-dependent decrease COX-2 expression and $PGE_2$ production in caveolin-1-transfected cells. Conclusion: Taken together, our data suggest that ectopic expression of caveolin-1 contributes to the expression and activity of COX-2 in articular chondrocytes through MAP kinase pathway.

• Journal of Periodontal and Implant Science
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• v.34 no.3
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• pp.489-498
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• 2004

Recent studies have demonstrated that human periodontal ligament cells express receptor activation of nuclear factor ${\kappa}B$ ligand (RANKL) which enhances the bone resorbing activity of osteoclasts differentiated from hematopoietic preosteoclasts. The purpose of this study is to determine the effects of p38 MAPK and JNK kinase upon regulating RANKL and OPG in response to $IL-1{\beta}$(l ng/ml) in rat periodontal ligament cells. Soluble RANKL was measured by immunoassay. The effects of p38 MAPK on RANKL and OPG expression was determined by RT-PCR. The results were as follows: 1. Periodontal ligament cells which stimulated by $IL-1{\beta}$ increased soluble RANKL synthesis by dose-dependent pattern. 2. p38 MAP kinase inhibitor (SB203580) showed regulation of soluble RANKL expression by dose-dependent manners. 3. p38 MAP kinase inhibitor (SB203580) regulated the expression of RANKL, but it dose regulate the expresseion of OPG. 4. JNK (c-jun $NH_2-terminal$ kinase) inhibitor (PD98059) did not regulate mRANKL and mOPG. These results suggested that p38 MAPK play a significant role in RANKL gene expression.