p38 MAPK and NF-κB mediate COX-2 expression in human airway myocytes

Singer, Cherie A.; Baker, Kimberly J.; McCaffrey, Alan; AuCoin, David P.; Dechert, Melissa A.; Gerthoffer, William T.

doi:10.1152/ajplung.00409.2002

Cited by 91 publications

(87 citation statements)

References 43 publications

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“…In human mesangial cells exposed to high glucose, in human monocytes undergoing differentiation, and in human fibroblasts subjected to cyclic stretch stimuli, increased COX-2 expression was dependent on generation of ROS (Amma et al 2005;Barbieri et al 2003;Kiritoshi et al 2003). These changes occurred through activation of p38 MAP kinase and a variety of transcription factors including NF-κB (Amma et al 2005;Kim et al 2005;Singer et al 2003). In the present study, 2244-TCB caused an increase in superoxide anion production, similar to results reported previously for rat neutrophils (Ganey et al 1993).…”

Section: Discussionsupporting

confidence: 89%

“…p38 regulates COX-2 expression both at the transcriptional level, by activating transcription factors, as well as at the level of RNA stability, by activating cytoplasmic proteins that increase the half life of COX-2 mRNA (Dean et al 1999;Lasa et al 2000;Singer et al 2003). In the present study, 2244-TCB exposure increased levels of phosphorylated, active p38 (Fig.…”

Section: Discussionsupporting

confidence: 60%

“…The link between p38 activity and changes in COX-2 expression has been well established in a variety of systems, including rat hepatic macrophages (Ahmad et al 2002), the HeLa cell line (Lasa et al 2000), human airway myocytes (Singer et al 2003) and human monocytes (Dean et al 1999). p38 regulates COX-2 expression both at the transcriptional level, by activating transcription factors, as well as at the level of RNA stability, by activating cytoplasmic proteins that increase the half life of COX-2 mRNA (Dean et al 1999;Lasa et al 2000;Singer et al 2003).…”

Section: Discussionmentioning

confidence: 99%

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2,2′,4,4′-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-κB

Bezdecny

Karmaus

Roth

et al. 2007

Toxicology and Applied Pharmacology

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Polychlorinated biphenyls (PCBs) are ubiquitous, persistent environmental contaminants that affect a number of cellular systems, including neutrophils. Among the effects caused by the noncoplanar PCB 2,2′,4,4′,-tetrachlorobiphenyl (2244-TCB) in granulocytic HL-60 cells are increases in superoxide anion production, activation of phospholipase A 2 with subsequent release of arachidonic acid (AA), and upregulation of the inflammatory gene cyclooxygenase-2 (COX-2). The objective of this study was to determine the signal transduction pathways involved in the upregulation of COX-2 by 2244-TCB. Treatment of HL-60 cells with 2244-TCB led to increased expression of COX-2 mRNA. This increase was prevented by the transcriptional inhibitor actinomycin D in cells pretreated with 2244-TCB for 10 minutes. The increase in COX-2 mRNA was associated with release of 3 H-AA, phosphorylation of p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinases, increased levels of nuclear NF-κB and increased superoxide anion production. Bromoenol lactone, an inhibitor of the calcium-independent phospholipase A 2 , reduced 3 H-AA release but had no effect on COX-2 mRNA, protein or activity. Pretreatment with SB-202190 or SB-203580, inhibitors of the p38 MAP kinase pathway, prevented the 2244-TCBmediated induction of COX-2 and phosphorylation of p38 and ERK MAP kinases. These inhibitors did not alter 3 H-AA release. Treatment with PD 98059 or U 0126, inhibitors of the MAP/ERK (MEK) pathway, prevented the 2244-TCB-mediated activation of ERK but had no effect on COX-2 induction or p38 phosphorylation. 2244-TCB treatment did not affect c-Jun N-terminal kinase (JNK) phosphorylation. 2244-TCB exposure increased the amount of nuclear NF-κB. This increase was prevented by pretreatment with p38 MAP kinase inhibitors, but not by pretreatment with MEK inhibitors. Pretreatment with inhibitors of NF-κB prevented the 2244-TCB-mediated induction of COX-2 mRNA. 2244-TCB-mediated increases in superoxide anion were prevented by the NADPH oxidase inhibitor apocynin or the free radical scavenger 4-hydroxy TEMPO, but neither of these inhibitors affected the 2244-TCB-induced changes in COX-2 mRNA levels or 3 H-AA release. Taken together these data suggest that p38 MAP kinase-dependent activation of NF-κB is critical for the 2244-TCB-mediated upregulation of COX-2 mRNA.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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2,2′,4,4′-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-κB

Bezdecny

Karmaus

Roth

et al. 2007

Toxicology and Applied Pharmacology

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“…7B). It is not clear how EGFR activity is increasing cox-2 expression, but future experiments will determine whether TNF-transactivated EGFR increases cox-2 transcription or regulates the stability of the mRNA through stabilizing factors such as the embryonic lethal abnormal vision (ELAV)-like HuR (15,61,65) or RNA-binding motif (RBM3) (66). Interestingly, TNF consistently stimulated more COX-2 protein induction than did EGF, but these ligands stimulated comparable levels of cox-2 mRNA.…”

Section: Discussionmentioning

confidence: 99%

TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells

Hobbs¹,

Goettel

Liang³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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TNF and epidermal growth factor (EGF) are well-known stimuli of cyclooxygenase (COX)-2 expression, and TNF stimulates transactivation of EGF receptor (EGFR) signaling to promote survival in colon epithelial cells. We hypothesized that COX-2 induction and cell survival signaling downstream of TNF are mediated by EGFR transactivation. TNF treatment was more cytotoxic to COX-2−/−mouse colon epithelial (MCE) cells than wild-type (WT) young adult mouse colon (YAMC) epithelial cells or COX-1−/−cells. TNF also induced COX-2 protein and mRNA expression in YAMC cells, but blockade of EGFR kinase activity or expression inhibited COX-2 upregulation. TNF-induced COX-2 expression was reduced and absent in EGFR−/−and TNF receptor-1 (TNFR1) knockout MCE cells, respectively, but was restored upon expression of the WT receptors. Inhibition of mediators of EGFR transactivation, Src family kinases and p38 MAPK, blocked TNF-induced COX-2 protein and mRNA expression. Finally, TNF injection increased COX-2 expression in colon epithelium of WT, but not kinase-defective EGFRwa2and EGFRwa5, mice. These data indicate that TNFR1-dependent transactivation of EGFR through a p38- and/or an Src-dependent mechanism stimulates COX-2 expression to promote cell survival. This highlights an EGFR-dependent cell signaling pathway and response that may be significant in colitis-associated carcinoma.

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“…The p38 MAPK kinase pathway, 49 the JNK pathway 50 and the NF-kB pathway 51 have all been implicated in the upregulation of COX-2 by IL-1b and TNFa. Most of the drugs that inhibit these kinases were products of the search for potent antiinflammatory agents that block the upregulation of COX-2 and thus block PGE 2 formation.…”

Section: Discussionmentioning

confidence: 99%

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity. OBJECTIVE: The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women. RESULTS: Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor a (TNFa) and IL-1b based on the ability of a combination of a soluble TNFa receptor (etanercept) and a blocking antibody against IL-1b to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor kB (NF-kB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogenactivated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-kB pathways was greater than that seen with only the NF-kB inhibitor. DISCUSSION: The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFa and Il-1b and involves the p38 MAPK and NF-kB pathways.

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p38 MAPK and NF-κB mediate COX-2 expression in human airway myocytes

Cited by 91 publications

References 43 publications

2,2′,4,4′-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-κB

2,2′,4,4′-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-κB

TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

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