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Inactive Rhomboid Protein 2 Mediates Intestinal Inflammation by Releasing Tumor Necrosis Factor-α

 Jee Hyun Kim  ;  Sung Wook Hwang  ;  Jaemoon Koh  ;  Jaeyoung Chun  ;  Changhyun Lee  ;  Jong Pil Im  ;  Joo Sung Kim 
 INFLAMMATORY BOWEL DISEASES, Vol.26(2) : 242-253, 2020-01 
Journal Title
Issue Date
Animals ; Carrier Proteins / physiology* ; Colitis / etiology* ; Colitis / pathology ; Cytokines ; Inflammation / etiology* ; Inflammation / metabolism ; Inflammation / pathology ; Intestines / drug effects ; Intestines / immunology* ; Intestines / pathology ; Lipopolysaccharides / pharmacology ; Macrophages / drug effects ; Macrophages / immunology* ; Macrophages / metabolism ; Macrophages / pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidative Stress ; Trinitrobenzenesulfonic Acid / toxicity ; Tumor Necrosis Factor-alpha / metabolism*
colitis ; inactive rhomboid protein 2 ; inflammatory bowel disease ; tumor necrosis factor-α
Background: Tumor necrosis factor (TNF)-α is a major proinflammatory cytokine that plays a key role in inflammatory bowel disease (IBD). Inactive rhomboid protein 2 (iRhom2) is essential for activating TNF-α-converting enzyme (TACE) in immune cells, which regulates TNF-α release. The aim of the study was to investigate the role of iRhom2 in intestinal inflammation in IBD. Methods: The expression of iRhom2 and TACE in lipopolysaccharide (LPS)-stimulated COLO 205 and RAW 264.7 cells was assessed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of iRhom2 and TACE in the colonic tissue of IBD patients and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-treated mice was determined by RT-PCR and immunohistochemistry. To assess the role of iRhom2 in intestinal inflammation, colitis was induced in wild-type and iRhom2-/- mice by the administration of TNBS enema. Results: In LPS-stimulated COLO 205 and RAW 264.7 cells, the mRNA and protein levels of TACE and iRhom2 were upregulated. The expression of TACE and iRhom2 in the colon of the IBD patients and TNBS-treated mice was significantly enhanced. The inflammatory cells that expressed high levels of iRhom2 in the colon were identified as macrophages. Finally, iRhom2 deficiency ameliorated TNBS-induced colitis by inhibiting TNF-α release. Conclusions: iRhom2 has an important role in intestinal inflammation through TNF-α secretion in immune cells, which suggests that iRhom2 could be a novel therapeutic target for IBD.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Chun, Jaeyoung(천재영) ORCID logo https://orcid.org/0000-0002-4212-0380
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