Exacerbating effects of PM2.5 in OVA-sensitized and challenged mice and the expression of TRPA1 and TRPV1 proteins in lungs

Abstract

ABSTRACTObjective: To investigate the effects of particulate matter ≤ 2.5 microns (PM2.5) on asthma-related phenotypes and on lung expression of TRPA1 and TRPV1 proteins in a mouse model of asthma. Methods: Female BALB/c mice were utilized to establish 28- and 42-day asthma models. Mice were sensitized with ovalbumin (OVA) and challenged with OVA, OVA plus normal saline (NS), or OVA plus PM2.5 at two doses, 1.6 or 8.0 mg kg−1. PM2.5 was instilled intratracheally without anesthesia. After the final OVA challenge was performed, 24 hours later, the changes in airway resistance (RI) and lung dynamic compliance (Cdyn) in response to acetylcholine chloride (ACH) were evaluated, and blood, bronchoalveolar lavage fluid (BALF) and lung tissue were taken at that time. The number of eosinophils in blood and various leukocytes in BALF were determined. Lung protein was extracted and probed for TRPA1 and TRPV1 expression. Interleukin (IL)-13, substance P (SP), prostaglandin D2 (PGD2) and nerve growth factor (NGF) in BALF were measured by enzyme-linked immunosorbent assay. Results: PM2.5 treated mice showed significantly greater changes in the number of inflammatory cells in blood and BALF, in RI and Cdyn in response to ACH, and in lung histopathology, indicated by inflammatory cell infiltration, thickened bronchial smooth muscles and bronchial mucosa damage, compared to controls. In addition, higher expression of TRPA1 and TRPV1 in lung and IL-13, SP, PGD2 and NGF in BALF were seen in mice exposed to PM2.5. All effects were most pronounced in mice in the 42-day model. Conclusions: PM2.5 exacerbates effects of asthma in this model, possibly by regulating TRPA1 and TRPV1 and the relevant neurokines.