Bisphenol A induces COX-2 through the mitogen-activated protein kinase pathway and is associated with levels of inflammation-related markers in elderly populations

• Published in: Environmental research Vol. 158; pp. 490 - 498
• Main Authors: Song, Heewon, Park, Joonwoo, Bui, Phuong T.C., Choi, KeunOh, Gye, Myung Chan, Hong, Yun-Chul, Kim, Jin Hee, Lee, Young Joo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.10.2017
• Subjects: Aged; Aged, 80 and over; alanine transaminase; aspartate transaminase; Benzhydryl Compounds - toxicity; Biomarkers - metabolism; Biomarkers - urine; Bisphenol A; blood serum; breast neoplasms; carcinogenesis; cell proliferation; COX-2 expression; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; elderly; endocrine-disrupting chemicals; epidemiological studies; Epidemiology; Female; genes; Humans; in vitro studies; Inflammation; Inflammation - metabolism; interleukin-10; leukocytes; Male; Middle Aged; mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - physiology; oxidative stress; Phenols - toxicity; phosphorylation; Republic of Korea; Signal Transduction; transcription factor NF-kappa B; tumor necrosis factor-alpha; urine; Bisphenol A; Inflammation; COX-2 expression; Epidemiology
• ISSN: 0013-9351; 1096-0953; 1096-0953
• DOI: 10.1016/j.envres.2017.07.005

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical, and it is one of the highest volume chemicals produced worldwide. Even though several in vivo and in vitro studies showed positive associations of BPA exposure with pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6, the mechanism by which BPA induces inflammation is unclear. We investigated the mechanism by which BPA induces inflammation (expression of inflammation-related genes, changes in oxidative stress, and cell proliferation and migration) and evaluated the effect of BPA exposure on inflammation-related markers in epidemiologic studies using repeat urine and serum samples from elderly subjects. BPA induced COX-2 expression via nuclear translocation of NF-κB and activation of mitogen-activated protein kinase (MAPK) by phosphorylation of ERK1/2 and enhanced the migration of lung cancer A549 and breast cancer MDAMB-231 cells. In two epidemiologic studies, we detected associations of BPA with six inflammation-related markers (WBC, CRP, IL-10, ALT, AST, and γ-GTP levels). Our findings probably suggest that BPA exposure induces inflammation and exacerbates tumorigenesis. •BPA induces COX-2 expression in lung cancer A549 and breast cancer MDAMB-231 cells.•Induction of COX-2 is through nuclear translocation of NF-κB and activation of MAPK.•BPA enhances the migration of A549 and MDAMB-231 cells.•Relations between BPA and inflammation-related markers were evaluated in elderly.•BPA exposure was associated with WBC, CRP, IL-10, ALT, AST, and γ-GTP levels.