Seung-Woo Han1, Jeong Min Kim2, Yunmee Lho3, Hyun Jung Cho4, Youn-Kwan Jung4, Jung-Ae Kim5, Hoyul Lee6, Yu-Jeong Lee6, Eun Soo Kim6. 1. Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. 2. Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Keimyung University, Daegu, Korea. 3. Department of Biochemistry, Pain Research Center, School of Medicine, Keimyung University, Daegu, Korea. 4. Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu, Korea. 5. College of Pharmacy, Yeungnam University, Daegu, Korea. 6. Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
Abstract
BACKGROUND: Adhesion molecules maintain the intestinal barrier function that is crucial to prevent intestinal inflammation. Dual immunoglobulin domain-containing adhesion molecule (DICAM) has been recently identified and known for the involvement in cell-cell adhesion through homophilic interaction and heterophilic interaction with integrin αVβ3. We tested whether the change of DICAM expression affects the severity of colonic inflammation. METHODS: Colitis was induced with oral administration of 2.5% dextran sulfate sodium (DSS) in 8-week-old male mice for 5 days. The function of DICAM under inflammatory condition was investigated using loss-of-function and gain-of-function models such as DICAM-deficient mice and adenoviral transduction of DICAM into Caco-2 colonic epithelial cells. RESULTS: DICAM increased in parallel with the degree of inflammation after 5-day administration of DSS and decreased with the resolution of inflammation. DICAM was expressed in the epithelial junctional complex and colocalized with ZO-1. Treatment with TNF-α or IFN-γ in Caco-2 cells significantly increased DICAM in protein and RNA level. The DICAM knockout mice showed more severe DSS-induced colitis compared with WT littermates. Adenoviral transduction of DICAM into Caco-2 cells significantly attenuated the inflammation-mediated decrease of adhesion molecules, including ZO-1 and occludin. Furthermore, Caco-2 cells with DICAM overexpression maintained intestinal barrier function under IFN-γ treatment as estimated by transepithelial electrical resistance. CONCLUSION: Our study demonstrates that DICAM which is increased in an inflammatory condition has a protective role in experimental colitis by stabilizing the integrity of junctional complex in the intestinal mucosal barrier.
BACKGROUND: Adhesion molecules maintain the intestinal barrier function that is crucial to prevent intestinal inflammation. Dual immunoglobulin domain-containing adhesion molecule (DICAM) has been recently identified and known for the involvement in cell-cell adhesion through homophilic interaction and heterophilic interaction with integrin αVβ3. We tested whether the change of DICAM expression affects the severity of colonic inflammation. METHODS:Colitis was induced with oral administration of 2.5% dextran sulfate sodium (DSS) in 8-week-old male mice for 5 days. The function of DICAM under inflammatory condition was investigated using loss-of-function and gain-of-function models such as DICAM-deficient mice and adenoviral transduction of DICAM into Caco-2 colonic epithelial cells. RESULTS:DICAM increased in parallel with the degree of inflammation after 5-day administration of DSS and decreased with the resolution of inflammation. DICAM was expressed in the epithelial junctional complex and colocalized with ZO-1. Treatment with TNF-α or IFN-γ in Caco-2 cells significantly increased DICAM in protein and RNA level. The DICAM knockout mice showed more severe DSS-induced colitis compared with WT littermates. Adenoviral transduction of DICAM into Caco-2 cells significantly attenuated the inflammation-mediated decrease of adhesion molecules, including ZO-1 and occludin. Furthermore, Caco-2 cells with DICAM overexpression maintained intestinal barrier function under IFN-γ treatment as estimated by transepithelial electrical resistance. CONCLUSION: Our study demonstrates that DICAM which is increased in an inflammatory condition has a protective role in experimental colitis by stabilizing the integrity of junctional complex in the intestinal mucosal barrier.
Authors: Arthur S Kim; Ofer Zimmerman; Julie M Fox; Christopher A Nelson; Katherine Basore; Rong Zhang; Lorellin Durnell; Chandni Desai; Christopher Bullock; Sharon L Deem; Jonas Oppenheimer; Beth Shapiro; Ting Wang; Sara Cherry; Carolyn B Coyne; Scott A Handley; Michael J Landis; Daved H Fremont; Michael S Diamond Journal: Cell Host Microbe Date: 2020-02-18 Impact factor: 21.023
Authors: Rong Zhang; James T Earnest; Arthur S Kim; Emma S Winkler; Pritesh Desai; Lucas J Adams; Gaowei Hu; Christopher Bullock; Beth Gold; Sara Cherry; Michael S Diamond Journal: Cell Rep Date: 2019-09-03 Impact factor: 9.423