Role of NF-kappaB/RelA and MAPK pathways in keratinocytes in response to sulfur mustard

The Journal of Investigative Dermatology
Bernd RebholzRudolf A Rupec

Abstract

Sulfur mustard (SM) is a strong vesicant that has been used as a chemical warfare agent. To understand the molecular mechanisms that underlie the inflammatory skin reaction in response to SM, we analyzed the activation pattern of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways. Keratinocytes responded with an induction of the canonical NF-kappaB pathway, including activation of IkappaB kinase 2, followed by phosphorylation and degradation of IkappaBalpha and of the transactivating subunit RelA at Ser536. The biphasic NF-kappaB response was strictly dependent on the transactivating subunit RelA, as demonstrated by keratinocytes lacking RelA. Parallel to NF-kappaB activation, we observed an induction of the Raf-1/MEK1/2/ERK1/2/MSK1 and MKK3/6/p38/MSK1 pathways. Although mitogen and stress-activated kinase 1 has been described as a RelA kinase with Ser276 as its target, this site remained unphosphorylated in response to SM. A further MAPK pathway induced by SM was the MKK4/7/JNK1/2 pathway, which resulted in phosphorylation of the transcription factor activating transcription factor-2, but not c-Jun. Our results indicate that SM induces a complex cellular response in keratinocytes, with the activation of three M...Continue Reading

References

Dec 10, 1991·Biochimica Et Biophysica Acta·P Angel, M Karin
Sep 1, 1988·Journal of the American Academy of Dermatology·L RequenaB Hernández-Moro
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·M TarutaniJ Takeda
Sep 20, 1997·The Journal of Biological Chemistry·X S WangZ Yao
Jan 31, 1998·The EMBO Journal·T MoriguchiE Nishida
Oct 16, 1999·The Journal of Biological Chemistry·H SakuraiW Toriumi
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Mar 10, 2001·Nature·L Chang, M Karin
May 23, 2001·International Immunopharmacology·Z M Hassan, M Ebtekar
Jun 13, 2001·Oncogene·W JochumE F Wagner
Nov 16, 2001·Biochemical and Biophysical Research Communications·I A Udalova, D Kwiatkowski
Oct 3, 2002·Nature Reviews. Immunology·Qiutang Li, Inder M Verma
Jan 16, 2004·Genes & Development·Jennifer Y ZhangPaul A Khavari
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Nov 24, 2004·Journal of Applied Toxicology : JAT·Mostafa Ghanei
Jan 18, 2005·Trends in Biochemical Sciences·Patrick ViatourAlain Chariot
Jan 28, 2005·Journal of Biochemical and Molecular Toxicology·James V RogersCarol L K Sabourin
Jan 28, 2005·Journal of Biochemical and Molecular Toxicology·Carol L K SabourinJohn J Schlager
May 25, 2005·Fundamental & Clinical Pharmacology·Mahdi Balali-Mood, Mehrdad Hefazi
Jun 28, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Gentzon HallTerry B Rogers
May 1, 1997·Expert Opinion on Investigational Drugs·A M Manning, F Mercurio
Aug 9, 2005·Toxicology·Kai Kehe, Ladislaus Szinicz
Sep 22, 2005·Nature Reviews. Immunology·Michael Karin, Florian R Greten
Aug 25, 2006·Journal of Virology·Danna HargettSteven L Bachenheimer
May 1, 2007·Biochemical Pharmacology·Catherine VerhaegheVincent Bours

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Citations

Oct 17, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Michael P ShakarjianJeffrey D Laskin
Jun 24, 2010·Inhalation Toxicology·Jeanclare SeagraveGary R Grotendorst
Dec 19, 2015·Drug and Chemical Toxicology·B Fatemeh Nobakht M GhDaryoush Hamidi Alamdari
Oct 31, 2012·Cutaneous and Ocular Toxicology·Albert Leonard RuffJames Franklin Dillman
May 26, 2009·Trends in Biochemical Sciences·Linda VermeulenGuy Haegeman
Feb 19, 2011·Critical Reviews in Toxicology·Kamyar GhabiliMohammadali M Shoja
Jul 16, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·E Chepchumba K Yego, James F Dillman
Feb 6, 2020·Toxicology Letters·Joanna A RuszkiewiczAswin Mangerich
Jul 31, 2012·Toxicology and Applied Pharmacology·Neera Tewari-SinghRajesh Agarwal

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