Analysis of SHIP1 expression and activity in Crohn’s disease patients

Rajesh Somasundaram; Sandra Fernandes; Jasper J. Deuring; Colin De Haar; Ernst J. Kuipers; Lauran Vogelaar; Frank A. Middleton; C. Janneke Van Der Woude; Maikel P. Peppelenbosch; William G. Kerr; Gwenny M. Fuhler

doi:10.1371/journal.pone.0182308

Analysis of SHIP1 expression and activity in Crohn’s disease patients

Rajesh Somasundaram, Sandra Fernandes, Jasper J. Deuring, Colin De Haar, Ernst J. Kuipers, Lauran Vogelaar, Frank A. Middleton, C. Janneke Van Der Woude, Maikel P. Peppelenbosch, William G. Kerr, Gwenny M. Fuhler^*

^*Corresponding author for this work

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

16 Citations (Scopus)

Abstract

Background: SH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn’s disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients. Methods: SHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880. Results: SHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort. Conclusions: Aberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.

Original language	English
Article number	e0182308
Journal	PLoS One
Volume	12
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0182308
Publication status	Published - Aug 2017
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2017 Somasundaram et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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title = "Analysis of SHIP1 expression and activity in Crohn{\textquoteright}s disease patients",

abstract = "Background: SH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn{\textquoteright}s disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients. Methods: SHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880. Results: SHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort. Conclusions: Aberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.",

author = "Rajesh Somasundaram and Sandra Fernandes and Deuring, {Jasper J.} and {De Haar}, Colin and Kuipers, {Ernst J.} and Lauran Vogelaar and Middleton, {Frank A.} and {Van Der Woude}, {C. Janneke} and Peppelenbosch, {Maikel P.} and Kerr, {William G.} and Fuhler, {Gwenny M.}",

note = "Publisher Copyright: {\textcopyright} 2017 Somasundaram et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2017",

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doi = "10.1371/journal.pone.0182308",

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AU - Somasundaram, Rajesh

AU - Fernandes, Sandra

AU - Deuring, Jasper J.

AU - De Haar, Colin

AU - Kuipers, Ernst J.

AU - Vogelaar, Lauran

AU - Middleton, Frank A.

AU - Van Der Woude, C. Janneke

AU - Peppelenbosch, Maikel P.

AU - Kerr, William G.

AU - Fuhler, Gwenny M.

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PY - 2017/8

Y1 - 2017/8

N2 - Background: SH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn’s disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients. Methods: SHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880. Results: SHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort. Conclusions: Aberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.

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Analysis of SHIP1 expression and activity in Crohn’s disease patients

Abstract

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