MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C

S C Corr; E M Palsson-McDermott; I Grishina; S P Barry; G Aviello; N J Bernard; P G Casey; J B J Ward; S J Keely; S Dandekar; P G Fallon; L A J O'Neill

doi:10.1038/mi.2013.24

MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C

S C Corr, E M Palsson-McDermott, I Grishina, S P Barry, G Aviello, N J Bernard, P G Casey, J B J Ward, S J Keely, S Dandekar, P G Fallon, L A J O'Neill

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

MyD88 adapter-like (Mal)-deficient mice displayed increased susceptibility to oral but not intraperitoneal infection with Salmonella Typhimurium. Bone marrow chimeras demonstrated that mice with Mal-deficient non-hematopoietic cells were more susceptible to infection, indicating a role for Mal in non-myeloid cells. We observed perturbed barrier function in Mal(-/-) mice, as indicated by reduced electrical resistance and increased mucosa blood permeability following infection. Altered expression of occludin, Zonula occludens-1, and claudin-3 in intestinal epithelia from Mal(-/-) mice suggest that Mal regulates tight junction formation, which may in part contribute to intestinal integrity. Mal interacted with several protein kinase C (PKC) isoforms in a Caco-2 model of intestinal epithelia and inhibition of Mal or PKC increased permeability and bacterial invasion via a paracellular route, while a pan-PKC inhibitor increased susceptibility to oral infection in mice. Mal signaling is therefore beneficial to the integrity of the intestinal barrier during infection.

Original language	English
Pages (from-to)	57-67
Number of pages	11
Journal	Mucosal Immunology
Volume	7
Issue number	1
Early online date	24 Apr 2013
DOIs	https://doi.org/10.1038/mi.2013.24
Publication status	Published - Jan 2014

Keywords

Animals
Cell Line
Gene Expression Regulation
Humans
Intestinal Mucosa
Intestines
Membrane Glycoproteins
Mice
Mice, Knockout
Permeability
Protein Binding
Protein Kinase C
Protein Transport
Receptors, Interleukin-1
Salmonella Infections
Salmonella typhimurium
Signal Transduction
Tight Junction Proteins
Journal Article
Research Support, Non-U.S. Gov't

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Corr, S. C., Palsson-McDermott, E. M., Grishina, I., Barry, S. P., Aviello, G., Bernard, N. J., Casey, P. G., Ward, J. B. J., Keely, S. J., Dandekar, S., Fallon, P. G., & O'Neill, L. A. J. (2014). MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. Mucosal Immunology, 7(1), 57-67. https://doi.org/10.1038/mi.2013.24

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abstract = "MyD88 adapter-like (Mal)-deficient mice displayed increased susceptibility to oral but not intraperitoneal infection with Salmonella Typhimurium. Bone marrow chimeras demonstrated that mice with Mal-deficient non-hematopoietic cells were more susceptible to infection, indicating a role for Mal in non-myeloid cells. We observed perturbed barrier function in Mal(-/-) mice, as indicated by reduced electrical resistance and increased mucosa blood permeability following infection. Altered expression of occludin, Zonula occludens-1, and claudin-3 in intestinal epithelia from Mal(-/-) mice suggest that Mal regulates tight junction formation, which may in part contribute to intestinal integrity. Mal interacted with several protein kinase C (PKC) isoforms in a Caco-2 model of intestinal epithelia and inhibition of Mal or PKC increased permeability and bacterial invasion via a paracellular route, while a pan-PKC inhibitor increased susceptibility to oral infection in mice. Mal signaling is therefore beneficial to the integrity of the intestinal barrier during infection.",

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AU - Barry, S P

AU - Aviello, G

AU - Bernard, N J

AU - Casey, P G

AU - Ward, J B J

AU - Keely, S J

AU - Dandekar, S

AU - Fallon, P G

AU - O'Neill, L A J

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AB - MyD88 adapter-like (Mal)-deficient mice displayed increased susceptibility to oral but not intraperitoneal infection with Salmonella Typhimurium. Bone marrow chimeras demonstrated that mice with Mal-deficient non-hematopoietic cells were more susceptible to infection, indicating a role for Mal in non-myeloid cells. We observed perturbed barrier function in Mal(-/-) mice, as indicated by reduced electrical resistance and increased mucosa blood permeability following infection. Altered expression of occludin, Zonula occludens-1, and claudin-3 in intestinal epithelia from Mal(-/-) mice suggest that Mal regulates tight junction formation, which may in part contribute to intestinal integrity. Mal interacted with several protein kinase C (PKC) isoforms in a Caco-2 model of intestinal epithelia and inhibition of Mal or PKC increased permeability and bacterial invasion via a paracellular route, while a pan-PKC inhibitor increased susceptibility to oral infection in mice. Mal signaling is therefore beneficial to the integrity of the intestinal barrier during infection.

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KW - Permeability

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KW - Salmonella typhimurium

KW - Signal Transduction

KW - Tight Junction Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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JO - Mucosal Immunology

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ER -

MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C

Abstract

Keywords

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