Thitima KasemsukSuttinee PhuagkhaopongRuedeemars YubolphanNorapat RungreangplangkoolPornpun VivithanapornFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityMahidol UniversityBurapha University2020-11-182020-11-182020-01-01Journal of Immunotoxicology. Vol.17, No.1 (2020), 186-193154769011547691X2-s2.0-85092939213https://repository.li.mahidol.ac.th/handle/20.500.14594/59997© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Cadmium (Cd) is accumulated in human astrocytes and induces the production of interleukin (IL)-6 and IL-8. Astrocytes are one of the major sources of chemokine C–C motif ligand 2 (CCL2; known as monocyte chemoattractant protein-1 [MCP-1]), in the brain. Elevated CCL2 levels are associated with cognitive impairment as well as the migration and invasion of glioblastoma cells. The present study hypothesized that non-toxic concentrations of Cd (as cadmium chloride [CdCl2]) could up-regulate CCL2 production in U-87 MG human glio-blastoma cells. The results showed that after exposure of the U-87 MG cells to CdCl2 at 1 and 10 µM, there was an up-regulation of CCL2 mRNA expression after 3 h of exposure and increased CCL2 secretion after 6 and 24 h. The study also found that inhibition of MAPK pathways, including ERK1/2, p38, and JNK by U0126, SB203580 and SP600125, respectively, reduced Cd-induced CCL2 secretion by the cells. Moreover, when cells were pretreated with Ro 32-0432 (an inhibitor of calcium-dependent PKC) and LY294002 (a PI3K inhibitor), this also resulted in a down-regulation of any Cd-induced CCL2 expression. Taken together, the results of this study allow for the conclusion to be made that CCL2 up-regulation in U-87 MG cells induced by Cd is mediated, in part, by an activation of MAPK, PI3K/Akt, and PKC pathways.Mahidol UniversityImmunology and MicrobiologyArticleSCOPUS10.1080/1547691X.2020.1829211