PMID- 35875256 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220726 IS - 2214-7500 (Electronic) IS - 2214-7500 (Linking) VI - 9 DP - 2022 TI - Microcystin-LR incorporated into colonic cells through probenecid-sensitive transporters leads to upregulated MCP-1 expression induced by JNK activation. PG - 937-944 LID - 10.1016/j.toxrep.2022.04.019 [doi] AB - Harmful algae that inhabit eutrophic lakes produce cyanotoxic microcystins. Therefore, the relationship between chronic exposure to microcystins via drinking water and organ disorders has been investigated. The present study aimed to determine whether representative microcystin-LR is involved in increased monocyte chemoattractant protein-1 (MCP-1) expression in rat colonic mucosa and enterocyte-like differentiated Caco-2 cells. The mRNA expression of MCP-1 was increased in the colons of rats administered with microcystin-LR, compared with controls. Furthermore, mRNA levels of MCP-1 expression significantly and positively correlated with those of Adhesion G Protein-Coupled Receptor E1 (ADGRE1; EMR1; F4/80), an indicator of macrophage infiltration, suggesting that increased MCP-1 expression induced by microcystin-LR promotes macrophage infiltration into the colon. Microcystin-LR increased MCP-1 expression in enterocyte-like differentiated Caco-2 cells, by activating c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK) or p38. The findings of transporter inhibitors indicated that microcystin-LR is incorporated into cells via ATP Binding Cassette (ABC) or solute carrier (SLC) transporters other than the organic anion transporting polypeptides (OATPs)1B1, 1B3, 2B1, and 1A2, which this leads to increased MCP-1 expression in the colon through activating JNK. Thus, increased MCP-1 expression induced by microcystin-LR might be a trigger for initiating tumorigenesis with inflammation in the colon because increased MCP-1 expression induces inflammation associated with macrophage infiltration into the colon, and chronic inflammation is associated with the initiation of tumorigenesis. CI - (c) 2022 The Authors. FAU - Koto, Yoshihito AU - Koto Y AD - Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. FAU - Kawahara, Hideaki AU - Kawahara H AD - Graduate School of Life and Environmental Science, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. FAU - Kurata, Koichi AU - Kurata K AD - Graduate School of Life and Environmental Science, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. FAU - Yoshikiyo, Keisuke AU - Yoshikiyo K AD - Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Graduate School of Life and Environmental Science, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. FAU - Hashiguchi, Ayumi AU - Hashiguchi A AD - Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Graduate School of Life and Environmental Science, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Institute of Environmental Systems Science, Academic Assembly, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Estuary Research Center, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. FAU - Okano, Kunihiro AU - Okano K AD - Faculty of Bioresource Sciences, Akita Prefectural University, Akita 010-0195, Japan. FAU - Sugiura, Norio AU - Sugiura N AD - Faculty of Life and Environmental Sciences, University of Tsukuba, Ibaraki 305-8572, Japan. FAU - Shimizu, Kazuya AU - Shimizu K AD - Faculty of Life Sciences, Toyo University, Gunma 374-0193, Japan. FAU - Shimizu, Hidehisa AU - Shimizu H AD - Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Graduate School of Life and Environmental Science, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Estuary Research Center, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Raman Project Center for Medical and Biological Applications, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Project Center for Fortification of Local Specialty Food Functions, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. AD - Interdisciplinary Center for Science Research, Shimane University, 1060 Nishikawatsu-Cho, Matsue, Shimane 690-8504, Japan. LA - eng PT - Journal Article DEP - 20220420 PL - Ireland TA - Toxicol Rep JT - Toxicology reports JID - 101630272 PMC - PMC9301606 OTO - NOTNLM OT - Colon OT - Cyanotoxin OT - JNK OT - MCP-1 OT - Microcystin OT - Probenecid COIS- No potential conflicts of interest are reported by the authors. EDAT- 2022/07/26 06:00 MHDA- 2022/07/26 06:01 PMCR- 2022/04/20 CRDT- 2022/07/25 04:07 PHST- 2021/09/27 00:00 [received] PHST- 2022/04/16 00:00 [revised] PHST- 2022/04/18 00:00 [accepted] PHST- 2022/07/25 04:07 [entrez] PHST- 2022/07/26 06:00 [pubmed] PHST- 2022/07/26 06:01 [medline] PHST- 2022/04/20 00:00 [pmc-release] AID - S2214-7500(22)00103-2 [pii] AID - 10.1016/j.toxrep.2022.04.019 [doi] PST - epublish SO - Toxicol Rep. 2022 Apr 20;9:937-944. doi: 10.1016/j.toxrep.2022.04.019. eCollection 2022.