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

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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.

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ACKNOWLEDGMENTS

This work was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01 DK072372]. We are grateful to Dr. Jorge Capdevila, Vanderbilt University for providing the Cyp4a-deficient mice that were used to establish our breeding colonies. The technical assistance of Mr. William Watkins, Dr. Matthew Merrell and Dr. Choon-Myung Lee is gratefully acknowledged. We wish to thank Dr. Dean P. Jones and Mr. Yongliang Liang (Clinical Biomarkers Laboratory, Department of Medicine, Emory University) for access to equipment used to quantify serum cytokines.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Emory University School of Medicine, 5119 Rollins Research Center, 1510 Clifton Road, Atlanta, GA, 30322, USA

    Beatrice A. Nyagode & Edward T. Morgan

  2. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Ifor R. Williams

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  1. Beatrice A. Nyagode
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Correspondence to Edward T. Morgan.

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Nyagode, B.A., Williams, I.R. & Morgan, E.T. Altered Inflammatory Responses to Citrobacter rodentium Infection, but not Bacterial Lipopolysaccharide, in Mice Lacking the Cyp4a10 or Cyp4a14 Genes. Inflammation 37, 893–907 (2014). https://doi.org/10.1007/s10753-013-9809-6

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