An inhibitor of p38 MAP kinase downregulates cytokine release induced by sulfur mustard exposure in human epidermal keratinocytes

Toxicology in Vitro : an International Journal Published in Association with BIBRA
James F DillmanJohn J Schlager

Abstract

Sulfur mustard (2,2'-dichlorodiethyl sulfide, SM) is a potent alkylating agent that induces skin vessication after cutaneous exposure. Previous work has revealed that SM induces the production of inflammatory cytokines, including IL-8, IL-6, TNF-alpha, and IL-1beta, in keratinocytes. The p38 MAP kinase (MAPK14) signaling pathway is activated via phosphorylation in response to cellular stress and has been implicated in the upregulation of cytokines in response to stress. We investigated the role of p38 MAP kinase in inflammatory cytokine upregulation following SM exposure. A dose response study in cultured human epidermal keratinocytes (HEK) revealed increasing phosphorylation of p38 MAP kinase in response to increasing concentrations of SM. A time course at the 200 microM exposure revealed that p38 MAP kinase phosphorylation is induced by 15 min post-exposure, peaks at 30 min and is sustained at peak levels until 8 h post-exposure. Phosphorylation of the upstream kinase MKK3/6 was also detected. Assay of the SM-exposed HEK culture media for cytokines revealed that exposure to 200 microM SM increased IL-8, IL-6, TNF-alpha, and IL-1beta. When cells exposed to 200 microM SM were treated with the p38 MAP kinase inhibitor SB203580, ...Continue Reading

References

Aug 24, 1999·Pharmacology & Therapeutics·J C LeeJ L Adams
Sep 22, 2000·The Biochemical Journal·S P DaviesP Cohen
Nov 18, 2000·Journal of Biochemical and Molecular Toxicology·C L SabourinR P Casillas
Jan 4, 2001·Journal of Applied Toxicology : JAT·J J Schlager, B W Hart

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Citations

Dec 17, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Neera Tewari-SinghRajesh Agarwal
Feb 19, 2011·Critical Reviews in Toxicology·Kamyar GhabiliMohammadali M Shoja
Sep 13, 2015·Cutaneous and Ocular Toxicology·Jennifer L PlahovinsakJohn S Graham
Jul 7, 2007·Drug and Chemical Toxicology·Jan OsterreicherJiri Kassa
Aug 17, 2010·Mathematical Biosciences·Qian YangIoannis P Androulakis
Dec 17, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·N M SayerC D Lindsay
Dec 27, 2008·Toxicology Letters·Claudia KaracsonyiElliott Kagan
Jul 8, 2008·Toxicology·Malgorzata DebiakAlexander Bürkle
Oct 30, 2007·Journal of Applied Toxicology : JAT·A O InmanJ E Riviere
Jul 12, 2008·Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine·Adam J SingerWexing Zong
Dec 12, 2007·Journal of Applied Toxicology : JAT·Christopher D LindsayJacques D Mathieu
Aug 26, 2010·Basic & Clinical Pharmacology & Toxicology·Min Tae KimSeon Jeong Kim
Jul 16, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·E Chepchumba K Yego, James F Dillman
Aug 4, 2016·Journal of Receptor and Signal Transduction Research·Mohammad Reza NouraniAbbas Ali Imani Fooladi
Jun 5, 2014·Annals of Saudi Medicine·Hamid NajmaddiniMojgan Noroozi Karimabad
Mar 12, 2019·The International Journal of Biological Markers·Eman A ToraihSomaya Hosny
Feb 6, 2020·Toxicology Letters·Joanna A RuszkiewiczAswin Mangerich
Nov 6, 2018·Chemico-biological Interactions·Georg MenacherTanja Popp
Oct 23, 2009·Chemical Research in Toxicology·Patrick A Everley, James F Dillman

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