Bisphenol AP promotes pulmonary fibrosis by regulating macrophage function in a bleomycin-induced mouse model.

Abstract

Bisphenols are extensively used in industrial and consumer products and may pose potential risks to human health. Previous studies have shown that bisphenol A (BPA) induces chronic inflammation and lung toxicity. Bisphenol AP (BPAP), a structural analogue of BPA, has also been associated with adverse health outcomes, including metabolic disorders and mood disturbances. However, its role in pulmonary diseases remains poorly characterized. In this study, a bleomycin (BLM)-induced pulmonary fibrosis (PF) model in C57BL/6 mice was employed to investigate the effects of BPAP on pulmonary pathology. Although BPAP exposure alone did not induce PF-related pathological changes, pretreatment with BPAP (0.4 mg/kg/day) initiated 14 days before BLM administration significantly aggravated BLM-induced histopathological alterations, inflammation, and collagen deposition. This exacerbation of fibrosis was accompanied by a marked upregulation of the M2 macrophage marker arginase-1. Further in vitro assays showed that 24-hour BPAP exposure inhibited macrophage proliferation, increased oxidative stress, and enhanced both phagocytic and chemotactic activities in the RAW 264.7 mouse macrophage cell line. Mechanistic analyses revealed that BPAP modulated several key molecules involved in cell cycle regulation, phagocytosis, and chemotaxis, specifically Ttk, Fcgr1, and Ccl5. These findings indicate that BPAP exacerbates BLM-induced PF by dysregulating macrophage function. This study provides new insights into the pulmonary toxicity of BPAP and underscores the potential health risks associated with its exposure.