PMID- 30908891 OWN - NLM STAT- MEDLINE DCOM- 20200708 LR - 20200708 IS - 2059-2310 (Electronic) IS - 2059-2302 (Linking) VI - 93 IP - 6 DP - 2019 Jun TI - Regulation of p38MAPK-mediated dendritic cell functions by the deubiquitylase otubain 1. PG - 462-470 LID - 10.1111/tan.13534 [doi] AB - Dendritic cells (DCs) are professional antigen presenting cells (APCs) that represent the essential link between innate and acquired immunity. Otubain (OTUB) 1 is shown to deubiquitinate TRAFs to suppress virus-induced inflammatory response. MAPK, a downstream molecule of TRAFs, is involved in regulating LPS-induced immune reactions and its activation is sensitive to the presence of OTUB1. Little is known about contributions of OTUB1 to changes in biological properties of DCs. The present study, therefore, explored whether DC functions are influenced by OTUB1. To this end, DCs were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs) and followed by treatment with lipopolysaccharide (LPS) in the presence or absence of OTUB1 siRNA. Expression of markers of cellular maturation and proliferation were analyzed by flow cytometry, and secretion of inflammatory cytokines and ability to stimulate CD4(+) T-cells in allogenic mixed leukocyte reaction (allo-MLR) by ELISA, cell migration by a transwell migration assay and phagocytic capacity by FITC-dextran uptake measurement. As a result, treatment of the cells with OTUB1 siRNA prolonged activation of p38MAPK, increased CD54 expression and IL-6 release and reduced FITC-dextran uptake. Moreover, cytokine release produced from CD4(+) T-cells in allo-MLR was different. The enhanced level of IFN-gamma, but not other cytokine production was observed in the presence of siRNA OTUB1. All the effects were completely abolished when the cells were exposed with p38MAPK inhibitor SB203580. In conclusion, OTUB1 prevents the prolonged activation of p38MAPK, which in turn compromises DC functions. CI - (c) 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Xuan, Nguyen Thi AU - Xuan NT AUID- ORCID: 0000-0003-3494-5136 AD - Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam. AD - Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam. FAU - Trung, Do Minh AU - Trung DM AD - Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi, Vietnam. FAU - Minh, Nghiem Ngoc AU - Minh NN AD - Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam. AD - Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam. FAU - Nghia, Vu Xuan AU - Nghia VX AD - Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam. FAU - Giang, Nguyen Van AU - Giang NV AD - Faculty of Biotechnology, Vietnam National University of Agriculture, Hanoi, Vietnam. FAU - Canh, Nguyen Xuan AU - Canh NX AD - Faculty of Biotechnology, Vietnam National University of Agriculture, Hanoi, Vietnam. FAU - Toan, Nguyen Linh AU - Toan NL AD - Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam. FAU - Cam, Truong Dinh AU - Cam TD AD - Department of Cardiology, 175 Military Medical Hospital, Ho Chi Minh, Vietnam. FAU - Nga, Nguyen Thanh AU - Nga NT AD - Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam. FAU - Tien, Tran Viet AU - Tien TV AD - Department of Infectious Diseases, 103 Hospital, Vietnam Military Medical University, Hanoi, Vietnam. FAU - Hoang, Nguyen Huy AU - Hoang NH AD - Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam. AD - Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam. LA - eng GR - 108.06-2017.16/Vietnam National Foundation for Science and Technology Development (NAFOSTED)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190404 PL - England TA - HLA JT - HLA JID - 101675570 RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Small Interfering) RN - 0 (interleukin-6, mouse) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Cysteine Endopeptidases) RN - EC 3.4.22.- (Otub1 protein, mouse) SB - IM MH - Animals MH - Bone Marrow Cells/cytology MH - CD4-Positive T-Lymphocytes/cytology MH - Cell Differentiation MH - Cell Movement MH - Cell Proliferation MH - Cells, Cultured MH - Cysteine Endopeptidases/*genetics/*metabolism MH - Dendritic Cells/*cytology MH - Intercellular Adhesion Molecule-1/metabolism MH - Interferon-gamma/metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharides MH - Mice MH - Mice, Inbred BALB C MH - Phagocytes/cytology MH - Phagocytosis MH - RNA, Small Interfering/genetics MH - Th17 Cells/cytology MH - p38 Mitogen-Activated Protein Kinases/*metabolism OTO - NOTNLM OT - LPS OT - dendritic cells OT - p38MAPK and otubain 1 EDAT- 2019/03/26 06:00 MHDA- 2020/07/09 06:00 CRDT- 2019/03/26 06:00 PHST- 2018/09/21 00:00 [received] PHST- 2019/02/13 00:00 [revised] PHST- 2019/03/21 00:00 [accepted] PHST- 2019/03/26 06:00 [pubmed] PHST- 2020/07/09 06:00 [medline] PHST- 2019/03/26 06:00 [entrez] AID - 10.1111/tan.13534 [doi] PST - ppublish SO - HLA. 2019 Jun;93(6):462-470. doi: 10.1111/tan.13534. Epub 2019 Apr 4.