Dataset Information

Chicken cathelicidin-B1, an antimicrobial guardian at the mucosal M cell gateway.

ABSTRACT: Mucosal epithelial M cells provide an efficient portal of entry for microorganisms. Initially defined by their irregular microvilli and abundant transcytotic channels in the avian bursa of Fabricius, M cells also are found in the lymphoid follicle-associated epithelium of the mammalian appendix, Peyer's patches, and other mucosal surface-lymphoid interfaces. We describe here a previously unrecognized cathelicidin gene in chickens, chCATH-B1, that is expressed exclusively in the epithelium of the bursa of Fabricius. Like the mature peptides of previously identified cathelicidins, the carboxyl-terminal peptide of chCATH-B1 has broad antimicrobial activity against Gram-positive and Gram-negative bacteria. chCATH-B1 expression is restricted to the secretory epithelial cell neighbors of the M cells, whereas its mature peptide is transported to become concentrated on the fibrillar network surrounding basolateral surfaces of the M cells that overlie the bursal lymphoid follicles. We conclude that chCATH-B1 is well placed to serve a protective antimicrobial role at the M cell gateway.

SUBMITTER: Goitsuka R

PROVIDER: S-EPMC1986613 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Chicken cathelicidin-B1, an antimicrobial guardian at the mucosal M cell gateway.

Goitsuka Ryo R Chen Chen-Lo H CL Benyon Lesley L Asano Yusuke Y Kitamura Daisuke D Cooper Max D MD

Proceedings of the National Academy of Sciences of the United States of America 20070907 38

Mucosal epithelial M cells provide an efficient portal of entry for microorganisms. Initially defined by their irregular microvilli and abundant transcytotic channels in the avian bursa of Fabricius, M cells also are found in the lymphoid follicle-associated epithelium of the mammalian appendix, Peyer's patches, and other mucosal surface-lymphoid interfaces. We describe here a previously unrecognized cathelicidin gene in chickens, chCATH-B1, that is expressed exclusively in the epithelium of the ...[more]

PMID: 17827276

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Project description:Cathelicidin-2 is an antimicrobial peptide (AMP) produced as part of the innate immune system of chickens and might be a new candidate to combat infection and inflammation within the gut-liver axis. Studying the hepatic immune response is of high importance as the liver is primarily exposed to gut-derived pathogen-associated molecular patterns. The aim of the present study was to assess the effects of chicken cathelicidin-2 alone or combined with lipoteichoic acid (LTA) or phorbol myristate acetate (PMA) on cell viability, immune response and redox homeostasis in a primary hepatocyte-non-parenchymal cell co-culture of chicken origin. Both concentrations of cathelicidin-2 decreased the cellular metabolic activity and increased the extracellular lactate dehydrogenase (LDH) activity reflecting reduced membrane integrity. Neither LTA nor PMA affected these parameters, and when combined with LTA, cathelicidin-2 could not influence the LDH activity. Cathelicidin-2 had an increasing effect on the concentration of the proinflammatory CXCLi2 and interferon- (IFN-)γ, and on that of the anti-inflammatory IL-10. Meanwhile, macrophage colony stimulating factor (M-CSF), playing a complex role in inflammation, was diminished by the AMP. LTA elevated IFN-γ and decreased M-CSF levels, while PMA only increased the concentration of M-CSF. Both concentrations of cathelicidin-2 increased the H2O2 release of the cells, but the concentration of malondialdehyde as a lipid peroxidation marker was not affected. Our findings give evidence that cathelicidin-2 can also possess anti-inflammatory effects, reflected by the alleviation of the LTA-triggered IFN-γ elevation, and by reducing the M-CSF production induced by PMA. Based on the present results, cathelicidin-2 plays a substantial role in modulating the hepatic immune response with a multifaceted mode of action. It was found to have dose-dependent effects on metabolic activity, membrane integrity, and reactive oxygen species production, indicating that using it in excessively high concentrations can contribute to cell damage. In conclusion, cathelicidin-2 seems to be a promising candidate for future immunomodulating drug development with an attempt to reduce the application of antibiotics.

Dataset Information

Chicken cathelicidin-B1, an antimicrobial guardian at the mucosal M cell gateway.

Publications

Chicken cathelicidin-B1, an antimicrobial guardian at the mucosal M cell gateway.

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