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Title: 2,2',4,4'-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-{kappa}B

Abstract

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{sub 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 min. The increase in COX-2 mRNA was associated with release of {sup 3}H-AA, phosphorylation of p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinases, increased levels of nuclear NF-{kappa}B and increased superoxide anion production. Bromoenol lactone, an inhibitor of the calcium-independent phospholipase A{sub 2}, reduced {sup 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-TCB-mediated induction of COX-2 and phosphorylation of p38 and ERK MAP kinases. These inhibitors did not alter {sup 3}H-AA release.more » 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-{kappa}B. This increase was prevented by pretreatment with p38 MAP kinase inhibitors, but not by pretreatment with MEK inhibitors. Pretreatment with inhibitors of NF-{kappa}B 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 {sup 3}H-AA release. Taken together these data suggest that p38 MAP kinase-dependent activation of NF-{kappa}B is critical for the 2244-TCB-mediated upregulation of COX-2 mRNA.« less

Authors:
 [1];  [1];  [1];  [2]
  1. Department of Pharmacology and Toxicology, Center for Integrative Toxicology and National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824 (United States)
  2. Department of Pharmacology and Toxicology, Center for Integrative Toxicology and National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824 (United States). E-mail: ganey@msu.edu
Publication Date:
OSTI Identifier:
20976957
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 221; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2007.03.019; PII: S0041-008X(07)00131-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTINOMYCIN; ANIONS; ARACHIDONIC ACID; INFLAMMATION; NEUTROPHILS; OXIDASES; PHOSPHORYLATION; PHOSPHOTRANSFERASES; POLYCHLORINATED BIPHENYLS; TRITIUM

Citation Formats

Bezdecny, Steven A., Karmaus, Peer, Roth, Robert A., and Ganey, Patricia E.. 2,2',4,4'-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-{kappa}B. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.03.019.
Bezdecny, Steven A., Karmaus, Peer, Roth, Robert A., & Ganey, Patricia E.. 2,2',4,4'-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-{kappa}B. United States. doi:10.1016/j.taap.2007.03.019.
Bezdecny, Steven A., Karmaus, Peer, Roth, Robert A., and Ganey, Patricia E.. Fri . "2,2',4,4'-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-{kappa}B". United States. doi:10.1016/j.taap.2007.03.019.
@article{osti_20976957,
title = {2,2',4,4'-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-{kappa}B},
author = {Bezdecny, Steven A. and Karmaus, Peer and Roth, Robert A. and Ganey, Patricia E.},
abstractNote = {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{sub 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 min. The increase in COX-2 mRNA was associated with release of {sup 3}H-AA, phosphorylation of p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinases, increased levels of nuclear NF-{kappa}B and increased superoxide anion production. Bromoenol lactone, an inhibitor of the calcium-independent phospholipase A{sub 2}, reduced {sup 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-TCB-mediated induction of COX-2 and phosphorylation of p38 and ERK MAP kinases. These inhibitors did not alter {sup 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-{kappa}B. This increase was prevented by pretreatment with p38 MAP kinase inhibitors, but not by pretreatment with MEK inhibitors. Pretreatment with inhibitors of NF-{kappa}B 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 {sup 3}H-AA release. Taken together these data suggest that p38 MAP kinase-dependent activation of NF-{kappa}B is critical for the 2244-TCB-mediated upregulation of COX-2 mRNA.},
doi = {10.1016/j.taap.2007.03.019},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 221,
place = {United States},
year = {Fri Jun 15 00:00:00 EDT 2007},
month = {Fri Jun 15 00:00:00 EDT 2007}
}
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