• Tuberculosis and Respiratory Diseases
• /
• 제53권6호
• /
• pp.595-611
• /
• 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.

• BMB Reports
• /
• 제47권12호
• /
• pp.685-690
• /
• 2014

The Ras/Raf/MEK/Erk signaling pathway is important for regulation of cell growth, proliferation, differentiation, survival, and apoptosis in response to a variety of extracellular stimuli. Lack of Erk MAPK activation is observed in several cancer cells despite active activation of Ras. However, little is known about the modulation of Erk1/2 activity by active Ras. Here, we show that overexpression of active H-Ras (H-RasG12R) in NIH3T3 fibroblasts impaired FGF2-induced Erk1/2 phosphorylation, as compared to wild-type cells. Northern blot analysis revealed that prolonged expression of active Ras increased MAP kinase phosphatase 3 (MKP3) mRNA expression, a negative regulator of Erk MAPK. Inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway abrogated active Ras-induced up-regulation of MKP3 expression, leading to the rescue of Erk1/2 phosphorylation. Our results demonstrated that the Ras/Raf/MEK/Erk signaling cascade is negatively regulated by the PI3K/Aktdependent transcriptional activation of the MKP3 gene.

• Molecules and Cells
• /
• 제24권1호
• /
• pp.9-15
• /
• 2007

To investigate the effects of chitosan on the redifferentiation of dedifferentiated chondrocytes, we used chondrocytes obtained from a micromass culture system. Micromass cultures of chick wing bud mesenchymal cells yielded differentiated chondrocytes, but these dedifferentiated during serial monolayer subculture. When the dedifferentiated chondrocytes were cultured on chitosan membranes they regained the phenotype of differentiated chondrocytes. Expression of protein kinase $C{\alpha}$ ($PKC{\alpha}$) increased during chondrogenesis, decreased during dedifferentiation, and increased again during redifferentiation. Treatment of the cultures with phorbol 12-myristate 13-acetate (PMA) inhibited redifferentiation and down-regulated $PKC{\alpha}$. In addition, the expression of p38 mitogen-activated protein (MAP) kinase increased during redifferentiation, and its inhibition suppressed redifferentiation. These findings establish a culture system for producing chondrocytes, point to a new role of chitosan in the redifferentiation of dedifferentiated chondrocytes, and show that $PKC{\alpha}$ and p38 MAP kinase activities are required for chondrocyte redifferentiation in this model system.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
• /
• pp.29-30
• /
• 2001

MAP kinase/ AP-1 signal transduction components are rapidly initiated by many extracellular stimuli, especially environmental carcinogens. We have investigated the role of MAP kinases (Erks, JNKs, and p38 kinases) and AP-1 signal transduction pathways in the process of cell transformation and carcinogenesis. Incubation of Cl 41 cells with tumor promoters such as TPA, EGF, arsenic, or TNF-$\alpha$ led to cell transformation and activation of MAP kinases.(omitted)

• Asian-Australasian Journal of Animal Sciences
• /
• 제16권8호
• /
• pp.1199-1204
• /
• 2003

The aim of this study was to investigate the role of phosphatidylinositol 3-kinase (PI3 kinase) and the mitogenactivating protein (MAP) kinase pathway on the differentiation of ovine preadipocytes. In order to investigate this issue, we monitored glycerol 3-phosphate dehydrogenase (GPDH) activity during differentiation with specific inhibitors of PI3 kinase and MAP kinase-Erk kinase, LY294002 and PD098059, respectively. The preadipocytes, which were obtained from ovine subcutaneous adipose tissues, were proliferated to confluence and then differentiated to adipocytes in differentiation medium with each inhibitor for 10 days. The confluent preadipocytes and differentiated adipocytes at days 3, 7 and 10 were harvested for assay of GPDH activity. LY294002 inhibited the differentiation program in dose- and day-dependent manners during 10 days of differentiation. PD098059 did not affect GPDH activity during differentiation. Furthermore, the expression of peroxisome proliferator-activated receptor ${\gamma}2$ (PPAR-${\gamma}2$), the representative early gene of differentiation, was markedly reduced by LY294002 treatment, although PD098059 did not change it. Our results demonstrated that the activation of PI3 kinase contributes to the differentiation process of ovine preadipocytes.

• 한국수의병리학회:학술대회논문집
• /
• 한국수의병리학회 2003년도 추계학술대회초록집
• /
• pp.42-42
• /
• 2003

The contamination of the environment with pollutants is one of the main problems of modern life, and the levels pollution in industrialized regions are giving raise to increased public concern. The mitogen-activated protein kinase (MAP kinase) are playa pivotal role in the regulation of important cellular functions by activation of specific signal transduction pathways from cell the surface to the nuclei. Three major subgroups of MAP kinases have been identified, and these comprise the extracellular signal-regulated kinase (ERK), the c-Jun amino-terminal kinase (JNK), and the p38 MAP kinases [1-3]. Herein, we investigated the effect of regulation of phospho-JNK (p-JNK), phospho-p38 (p-p38) and phospho-ERK (p-ERK) by TCDD. (omitted)

• 대한의생명과학회지
• /
• 제15권2호
• /
• pp.141-146
• /
• 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.

• 대한치과교정학회지
• /
• 제33권3호
• /
• pp.199-210
• /
• 2003

치아이동 시 발생하는 골흡수에서 이미 여러 cytokine의 중요성이 강조된 바 있으며 이 가운데 interleukin-6는 구강 및 연골조직 등에서 많은 연구의 초점이 되어 왔으나 확실한 기전은 아직까지 정확히 확립되어 있지 못하다 골흡수 시 조골세포에서 유리되는 interleukin-6 (IL-6)와 nitric oxide (NO) 등이 골흡수의 조절자로 최근 대두되고 있으며 Mitogen-activated Protein kinase (MAPK)의 활성화로 인해 염증성 cytokine등이 유리될 수 있음이 최근 macrophage 등에서 증명된 바 있다. 그러므로 치아이동을 비롯한 구강 내 여러 염증의 조건에서 골흡수의 대표인자인 IL-6및 NO유리가 MAPK등의 활성 등을 통해 조절될 수 있는 가능성을 시사하고 있다. 본 연구에서 조골세포 특징을 대부분 가지고 있는 조골세포주 MC3T3El에서 p-38 MAP kinase을 매개로 NO와 IL-6가 유리됨을 확인하고자 하였다. $10\%$ Fetal Bovine Serum이 첨가된 -MEM 배양액으로 배양한 조골세포주인 MC3T3El 세포에 tumor necrosis $factor-\alpha(TNF-\alpha)$, $interferon-\gamma(IFN-\gamma)$ 및 lipopolysacchalide(LPS) 등의 단독처리 시 NO와 IL-6의 증가는 확인되지 않았으나 $TNF-\alpha/IFN-\gamma$ 혹은 $LPS/IFN-\gamma$ 등의 처치시 NO와 IL-6의 유의한 증가를 보였으며, NO발현에 직접 관여하는 inducible nitric oxide synthase (iNOS)와 IL-6 단백질 및 mRNA의 발현을 관찰하였다. 또한 specific p-38 MAP kinase inhibitor인 SB203580의 NO와 IL-6의 생성 억제를 관찰하고 단백질과 mRNA발현억제를 통해서도 확인함으로써 SB203580은 transcription 단계에서 NO와 IL-6의 생성을 조절하고 있음을 시사하여 주고 있다. $TNF-\alpha/IFN-\gamma$ 혹은 $LPS/IFN-\gamma$ 처치 시 p-38 MAP Kinase의 활성을 관찰하였으나 단독 처치 시 역시 P-38 MAP Kinase의 활성을 확인함으로써 NO와 IL-6생성기전에는 p-38 MAP Kinase이외에 다른 인자 역시 관여하고 있음을 보여주고 있다. 본 연구에서는 치아 등의 골조직의 구성 세포인 조골세포에서 NO와 IL-6유리를 확인하였으며, 또한 이들의 생성기전중의 하나로 p-38 MAP Kinase가 transcription 단계에서 관여하고 있음을 확인하였다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제22권6호
• /
• pp.788-795
• /
• 2009

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis under various physiological and pathological conditions. We found that the VEGF isoforms VEGF120, VEGF164, and VEGF188 were expressed in the bovine mammary gland and bovine mammary epithelial cells (bMECs). Expression of VEGF in the mammary gland was significantly higher during the lactation period than during the dry period. Although dexamethasone or prolactin alone had little effect on the expression of VEGF, that in dexamethasone-treated cells was significantly induced after additional treatment with prolactin. Furthermore, the VEGF expression induced by the combination of dexamethasone and prolactin was reduced by PD98059 in a dose-dependent manner. This combination also stimulated the phosphorylation of p44/p42 MAP kinase in these cells. These results strongly suggest that the combination of dexamethasone and prolactin stimulates VEGF expression in bMECs via p44/p42 MAP kinase.

• Archives of Pharmacal Research
• /
• 제28권11호
• /
• pp.1257-1262
• /
• 2005

MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-$\alpha$ stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-$\alpha$ stimulation. To investigate the signaling pathway underlined in TNF-$\alpha$ induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-$\alpha$ treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-$\alpha$. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-$\alpha$ induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-$\alpha$. Taken together, we found that TNF-$\alpha$ stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.