NDLI: Tissue-Specific Regulation of p38 -Mediated Inflammation in Con A-Induced Acute Liver Damage.

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Tissue-Specific Regulation of p38 -Mediated Inflammation in Con A-Induced Acute Liver Damage.

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Tissue-Specific Regulation of p38 -Mediated Inflammation in Con A-Induced Acute Liver Damage.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bang, Bo-Ram Kang, Young Jun Otsu, Kinya Otsuka, Motoyuki
Description	Author Affiliation: Kang YJ ( Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037); Bang BR ( Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037); Otsuka M ( Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan); Otsu K ( Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan)
Abstract	Because p38 plays a critical role in inflammation, it has been an attractive target for the development of anti-inflammation therapeutics. However, p38 inhibitors showed side effects, including severe liver toxicity, that often prevailed over the benefits in clinical studies, and the mechanism of toxicity is not clear. In this study, we demonstrate that p38 regulates the inflammatory responses in acute liver inflammation in a tissue-specific manner, and liver toxicity by p38 inhibitors may be a result of the inhibition of protective activity of p38 in the liver. Genetic ablation of p38 in T and NKT cells protected mice from liver injury in Con A-induced liver inflammation, whereas liver-specific deletion of p38 aggravated liver pathology. We found that p38 deficiency in the liver increased the expression of chemokines to recruit more inflammatory cells, indicating that p38 in the liver plays a protective anti-inflammatory role during acute liver inflammation. Therefore, our results suggest that p38 regulates the inflammatory responses in a tissue-specific manner, and that the tissue-specific p38 targeting strategies can be used for the development of an effective anti-inflammation treatment with an improved side-effect profile.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1402954
Journal	The Journal of Immunology
Issue Number	10
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-05-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Liver Diseases Metabolism Liver Mitogen-activated Protein Kinase 14 Animals Concanavalin A Toxicity Disease Models, Animal Enzyme-linked Immunosorbent Assay Flow Cytometry Gene Knockout Techniques Immunoblotting Immunohistochemistry Inflammation Immunology Inflammation Mediators Mice Mice, Inbred C57bl Natural Killer T-cells Reverse Transcriptase Polymerase Chain Reaction T-lymphocytes Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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