PMID- 26263167 OWN - NLM STAT- MEDLINE DCOM- 20160620 LR - 20220311 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 28 IP - 1 DP - 2015 Sep TI - Anti-TNF-alpha monoclonal antibody reverses psoriasis through dual inhibition of inflammation and angiogenesis. PG - 731-43 LID - S1567-5769(15)30048-5 [pii] LID - 10.1016/j.intimp.2015.07.036 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) antagonists have shown remarkable efficacy in psoriasis; however, the precise mechanisms of action of TNF-alpha blocking agents mainly focus on their neutralizing TNF-alpha and its anti-inflammatory effects. In this study, we generated a humanized anti-TNF-alpha monoclonal antibody (IBI303) and suggested a potential mechanism of anti-TNF-alpha therapy for psoriasis. The results of SPR and ELISA indicated that IBI303 has a good affinity to TNF-alpha. In vitro, it could suppress TNF-alpha-induced cytotoxicity in WEHI164 cells. In vivo, administration of IBI303 to K14-VEGF transgenic mice led to a significant treatment efficiency in psoriasis in a dose-dependent manner. IHC staining and cytokines-ELISA indicated that TNF-alpha inhibition strongly reduced inflammatory cells infiltration and pro-inflammatory cytokines release, accompanied by suppression of inflamed dermal blood vessels. Mechanistically, in order to explain the anti-angiogenesis effect of anti-TNF-alpha antibody, the production of cytokine in macrophage conditional medium was measured by ELISA. The result indicated that the massive secretion of TNF-alpha stimulated by LPS in RAW264.7 cell supernatant was markedly neutralized in a dose-response manner by IBI303, moreover, the expression of NF-kappaB p65 was down-regulated. Mouse endothelial cell tube formation assay showed that anti-TNF-alpha could inhibit blood vessels formation directly and indirectly. Collectively, our study suggested a kind of antipsoriatic mechanism of TNF-alpha inhibitors that is the dual inhibition of inflammation and angiogenesis. CI - Copyright (c) 2015. Published by Elsevier B.V. FAU - Liu, Yu AU - Liu Y AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Yang, Guoyou AU - Yang G AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Zhang, Junfeng AU - Zhang J AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Xing, Kaiyan AU - Xing K AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Dai, Lei AU - Dai L AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Cheng, Lin AU - Cheng L AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Liu, Junli AU - Liu J AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Deng, Jie AU - Deng J AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Shi, Gang AU - Shi G AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Li, Chunlei AU - Li C AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China; Chongqing Tree Gorges Medical College, Faculty of Basic Medicine, Department of Biochemistry, People's Republic of China. FAU - Su, Xiaolan AU - Su X AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Zhang, Shuang AU - Zhang S AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Yang, Yang AU - Yang Y AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Li, Jia AU - Li J AD - Innovent Biologics, Inc., Suzhou, Jiangsu, People's Republic of China. FAU - Yu, Dechao AU - Yu D AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China; Innovent Biologics, Inc., Suzhou, Jiangsu, People's Republic of China. FAU - Xiang, Rong AU - Xiang R AD - Department of Immunology, Nankai University School of Medicine, Tianjin, People's Republic of China. FAU - Wei, Yuquan AU - Wei Y AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. FAU - Deng, Hongxin AU - Deng H AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China. Electronic address: denghongx@scu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150807 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Cytokines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM EIN - Int Immunopharmacol. 2020 Nov;88:107019. PMID: 33182062 MH - Angiogenesis Inhibitors/administration & dosage/*therapeutic use MH - Animals MH - Anti-Inflammatory Agents/administration & dosage/*therapeutic use MH - Antibodies, Monoclonal, Humanized/administration & dosage/*therapeutic use MH - Cell Culture Techniques MH - Cell Line, Tumor MH - Cytokines/immunology/metabolism MH - Macrophages/drug effects/immunology MH - Mice, Transgenic MH - Neovascularization, Physiologic/*drug effects/immunology MH - Psoriasis/*drug therapy/immunology MH - Skin/blood supply/drug effects/immunology MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/immunology MH - Vascular Endothelial Growth Factor A/genetics OTO - NOTNLM OT - Angiogenesis OT - Anti-psoriatic therapy OT - Inflammation OT - K14-VEGF transgenic mice OT - Tumor necrosis factor-alpha (TNF-alpha) EDAT- 2015/08/12 06:00 MHDA- 2016/06/21 06:00 CRDT- 2015/08/12 06:00 PHST- 2015/04/08 00:00 [received] PHST- 2015/05/28 00:00 [revised] PHST- 2015/07/27 00:00 [accepted] PHST- 2015/08/12 06:00 [entrez] PHST- 2015/08/12 06:00 [pubmed] PHST- 2016/06/21 06:00 [medline] AID - S1567-5769(15)30048-5 [pii] AID - 10.1016/j.intimp.2015.07.036 [doi] PST - ppublish SO - Int Immunopharmacol. 2015 Sep;28(1):731-43. doi: 10.1016/j.intimp.2015.07.036. Epub 2015 Aug 7.