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

• Published in: PloS one Vol. 12; no. 8; p. e0182308
• Main Authors: Somasundaram, Rajesh, Fernandes, Sandra, Deuring, Jasper J., de Haar, Colin, Kuipers, Ernst J., Vogelaar, Lauran, Middleton, Frank A., van der Woude, C. Janneke, Peppelenbosch, Maikel P., Kerr, William G., Fuhler, Gwenny M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.08.2017; Public Library of Science (PLoS)
• Subjects: Aberration; Adaptive immunity; Adult; Authorship; Autophagy-Related Proteins - genetics; Biology and Life Sciences; Biopsy; Bone marrow; Cell Line; Cohort Studies; Correlation; Crohn Disease - genetics; Crohn Disease - metabolism; Crohn's disease; Deoxyribonucleic acid; Deregulation; DNA; Down-Regulation; Female; Fibrosis; Gastroenterology; Gene expression; Gene Expression Regulation; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Hepatology; Humans; Ileitis; Immune response; Immunity; Immunology; Inflammatory bowel disease; Inositol; Inositol-1,4,5-trisphosphate 5-phosphatase; Intestine; Leukocytes (mononuclear); Malachite green; Male; Medicine and Health Sciences; Mice; Middle Aged; Patients; People and Places; Peripheral blood mononuclear cells; Phosphatase; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases - genetics; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases - metabolism; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Remission; Research and Analysis Methods; Single-nucleotide polymorphism; Small intestine; Western blotting; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182308

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. 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. 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. Aberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.