Mono(2-ethylhexyl) phthalate modulates bone marrow-derived APCs and exacerbates allergic lung inflammation via PPARγ-dependent pro-inflammatory signaling

BACKGROUND: approaches. METHODS: , granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated bone marrow-derived antigen-presenting cells (BM-APCs) were treated with MEHP, with or without PPARγ antagonist or agonist. Surface marker expression and cytokine production were evaluated by flow cytometry and ELISA, and IκBα phosphorylation was assessed by immunoblotting. RESULTS: , MEHP-treated BM-APCs showed increased IL-6 and IL-12 production, along with reduced IL-10, MHC class II, and CD86 expression. These effects were partially reversed by a modulator of peroxisome proliferator-activated receptor gamma (PPARγ) antagonist and recapitulated by a PPARγ agonist. MEHP also induced IκBα phosphorylation, suggesting activation of NF-κB independently of PPARγ. CONCLUSION: Mechanistically, our findings indicate that MEHP modulates APC cytokine profiles and surface phenotype through both PPARγ-dependent and -independent pathways. MEHP exposure aggravated lung inflammation and increased IgE levels at TDI-equivalent doses, supporting its pathogenic potential under physiologically relevant conditions.