PMID- 29197248 OWN - NLM STAT- MEDLINE DCOM- 20180416 LR - 20201209 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 194 DP - 2018 Mar TI - The role of IL-8/CXCR2 signaling in microcystin-LR triggered endothelial cell activation and increased vascular permeability. PG - 43-48 LID - S0045-6535(17)31897-0 [pii] LID - 10.1016/j.chemosphere.2017.11.120 [doi] AB - Microcystins are a family of cyclic heptapeptide toxins naturally produced by freshwater cyanobacteria. Microcystin-LR (MCLR) is believed to be the most toxic and common one with various pathological effects on human and mammals. However, the effects of MCLR on endothelial cells and vascular homeostasis have been largely unknown. We explored the mRNA and protein expression changes of several pro-inflammatory mediators in human umbilical vein endothelial cells (HUVECs) and C57BC/6 mice exposed to MCLR. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), especially interleukin-8 (IL-8) were remarkably upregulated both in endothelial cells and in serum. Increased endothelial permeability in vitro and chronic microvascular permeability in animals were also observed. Silencing the IL-8 gene with siRNA or blocking its cognate receptor, CXC-chemokine receptor type 2 (CXCR2), by a specific inhibitor efficiently prevented the MCLR induced leakage. These observations indicate a novel insight of inflammation triggered property of MCLR via IL-8/CXCR2 signaling, suggesting CXCR2 as a target molecule in protective strategy against the wide range pollution of microcystin. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Chen, Limei AU - Chen L AD - Department of Marine Ecology, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China; School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China. Electronic address: chenlimei2005@163.conm. FAU - Liu, Xiaoying AU - Liu X AD - School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China. Electronic address: xiaoying6690@163.com. FAU - Pan, Zhifang AU - Pan Z AD - School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China. Electronic address: pzhifang@163.com. FAU - Liu, Shunmei AU - Liu S AD - School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China. Electronic address: bio-shunmei@163.com. FAU - Han, Huirong AU - Han H AD - School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China. Electronic address: hanhuirong@wfmc.edu.cn. FAU - Zhao, Chunling AU - Zhao C AD - School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China. Electronic address: zhaochunlingbj@163.com. FAU - Tang, Xuexi AU - Tang X AD - Department of Marine Ecology, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China. Electronic address: tangxx@ouc.edu.cn. LA - eng PT - Journal Article DEP - 20171125 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Marine Toxins) RN - 0 (Microcystins) RN - 0 (Receptors, Interleukin-8B) RN - 0 (Tumor Necrosis Factor-alpha) RN - EQ8332842Y (cyanoginosin LR) SB - IM MH - Animals MH - Capillary Permeability/*drug effects MH - Cyanobacteria/metabolism/pathogenicity MH - Human Umbilical Vein Endothelial Cells/*metabolism MH - Humans MH - Inflammation/complications/etiology MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Interleukin-8/genetics/*metabolism MH - Marine Toxins MH - Mice MH - Microcystins/*pharmacology MH - Receptors, Interleukin-8B/*metabolism MH - Signal Transduction/drug effects MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - IL-8/CXCR2 signal OT - Microcystin-LR OT - Pro-inflammatory mediators OT - Vascular permeability EDAT- 2017/12/03 06:00 MHDA- 2018/04/17 06:00 CRDT- 2017/12/03 06:00 PHST- 2017/08/19 00:00 [received] PHST- 2017/11/06 00:00 [revised] PHST- 2017/11/21 00:00 [accepted] PHST- 2017/12/03 06:00 [pubmed] PHST- 2018/04/17 06:00 [medline] PHST- 2017/12/03 06:00 [entrez] AID - S0045-6535(17)31897-0 [pii] AID - 10.1016/j.chemosphere.2017.11.120 [doi] PST - ppublish SO - Chemosphere. 2018 Mar;194:43-48. doi: 10.1016/j.chemosphere.2017.11.120. Epub 2017 Nov 25.