Altered Inflammatory Responses to Citrobacter rodentium Infection, but not Bacterial Lipopolysaccharide, in Mice Lacking the Cyp4a10 or Cyp4a14 Genes

• Type of Material: Article
• Authors: Beatrice A. Nyagode, Emory University; Ifor Williams, Emory University; Edward T Morgan, Emory University
• Language: English
• Date: 2014-06-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Springer Science+Business Media.
• Final Published Version (URL): http://dx.doi.org/10.1007/s10753-013-9809-6
• Title of Journal or Parent Work: Inflammation
• ISSN: 0360-3997
• Volume: 37
• Issue: 3
• Start Page: 893
• End Page: 907
• Grant/Funding Information: This work was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01 DK072372].
• Keywords: Cyp4a; Science & Technology; fatty acids; LPS; CYTOCHROMES P450; C. rodentium; KIDNEY; MODULATION; PROLIFERATOR-ACTIVATED RECEPTOR; Life Sciences & Biomedicine; ARACHIDONIC-ACID; acute phase proteins; EXPRESSION; ALPHA; Immunology; Cell Biology; 20-HYDROXYEICOSATETRAENOIC ACID; DOWN-REGULATION; MOUSE
• Research Categories: Biology, Cell; Health Sciences, Immunology

Abstract

Murine hepatic Cyp4a mRNAs are markedly downregulated during inflammation. Here, we investigated the roles of Cyp4a10 and Cyp4a14 in the response to infection with C. rodentium. Absence of either Cyp4a gene attenuated or abrogated the changes in spleen weight, colon crypt length, hepatic cytokine, and acute phase protein mRNAs, and serum acute phase proteins and cytokines caused by infection. Cyp4a10-/- mice on a low-salt diet had a similar hepatic acute phase response as those mice on a high-salt diet, suggesting that hypertension associated with this genotype is not the cause of their altered inflammatory response. In contrast, wild-type, Cyp4a10-/-, and Cyp4a14-/- mice showed similar responses to injected LPS. These results implicate Cyp4a10 and Cyp4a14 in the regulation of the host inflammatory response to enteropathogenic bacterial infection but not to acute aseptic inflammation. Understanding the mechanism of this role may lead to novel therapeutic approaches in some inflammatory diseases.