Role of JNK in hypertonic activation of Cl−-dependent Na+/H+ exchange in Xenopus oocytes

Goss, Greg G.; Jiang, Liang; Vandorpe, David H.; Kieller, Dawn M.; Chernova, Marina N.; Robertson, MM; Alper, Seth L.

doi:10.1152/ajpcell.2001.281.6.c1978

Cited by 36 publications

(18 citation statements)

References 63 publications

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“…In this study, we also tested SP600125, a widely used JNK inhibitor in cell-based assays (4,14,32), to inhibit JNK activation and the subsequent regulation of cytokine production. We found that SP600125 had a potent inhibitory effect on JNK phosphorylation; however, it also inhibited rHagB-induced ERK phosphorylation, at least at concentrations greater than 1 M, and had a suppressive effect on the production of all the tested cytokines at concentrations higher than 1 M (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Role of Mitogen-Activated Protein Kinases and NF-κB in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines byPorphyromonas gingivalisHemagglutinin B

Zhang¹,

Martin²,

Michalek

et al. 2005

Infect Immun

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Hemagglutinin B (HagB) is a nonfimbrial adhesin expressed on the surface of Porphyromonas gingivalis and has been implicated as a potential virulence factor involved in mediating the attachment of the bacteria to host cells. However, the molecular mechanisms underlying host responses to HagB and their roles in pathogenesis have yet to be elucidated. Mitogen-activated protein kinases (MAPKs) are activated following engagement of a variety of cell surface receptors via dual tyrosine and threonine phosphorylation and are thought to be involved in various cellular responses. The purpose of this study was to determine the role of intracellular signaling pathways including the MAPKs and NF-B in regulating the production of proinflammatory and anti-inflammatory cytokines following stimulation of murine macrophages with recombinant HagB (rHagB). Stimulation of peritoneal macrophages with rHagB resulted in the production of the proinflammatory cytokines interleukin-12p40 (IL-12p40), gamma interferon (IFN-␥), and tumor necrosis factor alpha, as well as the anti-inflammatory cytokine IL-10. We also demonstrated the activation of extracellular signal-related kinase (ERK), c-Jun NH 2 -terminal protein kinase (JNK), and p38 MAPKs by rHagB-stimulated macrophages. Furthermore, blocking of the ERK and p38 signaling pathways by using specific inhibitors revealed differential regulatory roles in the rHagB-mediated production of proinflammatory and anti-inflammatory cytokines. ERK and p38 were important in down-regulation of IL-12p40 and IFN-␥ production and up-regulation of IL-10 production. The enhanced levels of IL-12p40 in rHagB-stimulated macrophages by inhibition of ERK or p38 activity were partially attributable to the inhibition of IL-10 production. Moreover, NF-B was found to be critical for up-regulation of IL-12p40 and down-regulation of IL-10 production in rHagB-stimulated macrophages. Taken together, our results demonstrate a role for the p38 and ERK pathways and the transcription factor NF-B in modulating key immunoregulatory cytokines involved in the development of immune responses to P. gingivalis HagB.

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Section: Discussionmentioning

confidence: 99%

Role of Mitogen-Activated Protein Kinases and NF-κB in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines byPorphyromonas gingivalisHemagglutinin B

Zhang¹,

Martin²,

Michalek

et al. 2005

Infect Immun

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“…Specific JNK inhibitors [16][17][18][19], CC0209766, CC0223105, and CC-401 were synthesized by Signal Pharmaceuticals, Inc. Each JNK inhibitor is dissolved in vehicle before injection (5% 1-methyl-2-pyrrolidone, 30% PEG-400, 25% PEG-200, 20% propylene glycol, USP, 20% 0.9% sodium chloride for injection, USP). JNK inhibitors (3-20 mg/kg rat, dissolved in 0.6-8.0 mg/ml vehicle) or equivalent volume of vehicle only are administrated intravenously at 15 min before starting ischemia.…”

Section: Reagentsmentioning

confidence: 99%

JNK mediates hepatic ischemia reperfusion injury

Uehara

Bennett²,

Sakata³

et al. 2005

Journal of Hepatology

199

138

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“…MAPKs have been implicated in shrinkageinduced NHE1 activation in some cell types [20,21], yet not in others [22]. Interestingly, recent studies have assigned a role for NHE1 upstream of activation of ERK1/2 after exposure to angiotensin II or 5-HT [23], as well as after cardiomyocyte stretch [24].…”

Section: Introductionmentioning

confidence: 99%

The Na+/H+ Exchanger, NHE1, Differentially Regulates Mitogen-Activated Protein Kinase Subfamilies after Osmotic Shrinkage in Ehrlich Lettre Ascites Cells

Pedersen¹,

Darborg²,

Rasmussen³

et al. 2007

Cell Physiol Biochem

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Osmotic stress modulates mitogen activated protein kinase (MAPK) activities, leading to altered gene transcription and cell death/survival balance, however, the mechanisms involved are incompletely elucidated. Here, we show, using a combination of biochemical and molecular biology approaches, that three MAPKs exhibit unique interrelationships with the Na⁺/H⁺ exchanger, NHE1, after osmotic cell shrinkage: Extracellular Signal Regulated Kinase (ERK1/2) is inhibited in an NHE1-dependent, pH_i-independent manner, c-Jun N-terminal kinase (JNK1/2) is stimulated, in part through NHE1-mediated intracellular alkalinization, and p38 MAPK is activated in an NHE1-independent manner, and contributes to NHE1 activation and ERK inhibition. Shrinkage-induced ERK1/2 inhibition was attenuated in Ehrlich Lettre Ascites cells by NHE1 inhibitors (EIPA, cariporide) or removal of extracellular Na⁺, and mimicked by human (h) NHE1 expression in cells lacking endogenous NHE1 activity. The effect of NHE1 on ERK1/2 was pH_i-independent and upstream of MEK1/2. Shrinkage-activation of JNK1/2 was attenuated by EIPA, augmented by hNHE1 expression, and abolished in the presence of HCO₃^-. Basal JNK activity was augmented at alkaline pH_i. Shrinkage-activation of p38 MAPK was NHE1-independent, and p38 MAPK inhibition (SB203580) attenuated NHE1 activation and ERK1/2 inhibition. Long-term shrinkage elicited caspase-3 activation and a loss of cell viability, which was augmented by ERK1/2 or JNK1/2 inhibition, and attenuated by p38 MAPK inhibition.

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Role of JNK in hypertonic activation of Cl⁻-dependent Na⁺/H⁺ exchange in Xenopus oocytes

Cited by 36 publications

References 63 publications

Role of Mitogen-Activated Protein Kinases and NF-κB in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines byPorphyromonas gingivalisHemagglutinin B

Role of Mitogen-Activated Protein Kinases and NF-κB in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines byPorphyromonas gingivalisHemagglutinin B

JNK mediates hepatic ischemia reperfusion injury

The Na<sup>+</sup>/H<sup>+</sup> Exchanger, NHE1, Differentially Regulates Mitogen-Activated Protein Kinase Subfamilies after Osmotic Shrinkage in Ehrlich Lettre Ascites Cells

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