title: Mono-(2-ethylhexyl) phthalate-induced Sertoli cell injury stimulates the production of pro-inflammatory cytokines in Fischer 344 rats.
abstract: Exposure of rodents to the Sertoli cell (SC) toxicant mono-(2-ethylhexyl) phthalate (MEHP) has been reported to trigger an infiltration of macrophages into the testis in an age- and species-dependent manner. Here we challenge the hypothesis that the peripubertal rat-specific infiltration of macrophages after MEHP exposure is due, in part, to an increase in SC-specific inflammatory cytokine expression. To rule out that germ cell(GC) apoptosis itself is responsible for macrophage recruitment, rats were exposed to a direct GC toxicant, methoxyacetic acid (MAA), but no infiltration of macrophages was observed. Next, mRNA levels of inflammatory cytokines were evaluated after MEHP exposure. IL-1α, IL-6, and MCP-1 expression were increased in vivo and correlated with macrophage infiltration in a species-specific manner. Additionally, IL-6 and MCP-1 expression was increased in SC-GC co-cultures and ASC-17D SCs. These results indicate that MEHP-injury in pubertal rats specifically stimulates secretion of pro-inflammatory cytokines and alters the immune microenvironment.
authors.affiliation: Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Stermer
authors.affiliation: Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Caitlin J
authors.initials: CJ
authors.lastname: Murphy
authors.affiliation: Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Rashin
authors.initials: R
authors.lastname: Ghaffari
authors.affiliation: Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Di Bona
authors.affiliation: Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Jorine J
authors.initials: JJ
authors.lastname: Voss
authors.affiliation: Center for Molecular Carcinogenesis and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, United States. Electronic address: john.richburg@austin.utexas.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Richburg
mesh_terms: D000085:Acetates / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D011916:Rats, Inbred F344; D012708:Sertoli Cells / Q000187:drug effects* / Q000276:immunology; D013045:Species Specificity
chemical_list: D000085:Acetates; D016207:Cytokines; D052244:Endocrine Disruptors; D012333:RNA, Messenger; D004051:Diethylhexyl Phthalate; C013598:methoxyacetic acid; C016599:mono-(2-ethylhexyl)phthalate
keywords: Cytokines; Mono-(2-ethylhexyl) phthalate; Sertoli cells; Testicular macrophages