Oxidative Stress and Asthma: Proteome Analysis of Chitinase-like Proteins and FIZZ1 in Lung Tissue and Bronchoalveolar Lavage Fluid

摘要

Oxidative stress plays an important role in the development of airway inflammation and hyperreactivity in asthma. The identification of oxidative stress markers in bronchoalveolar lavage fluid (BALF) and lung tissue from ovalbumin (OVA) sensitized mice could provide new insight into disease pathogenesis and possible use of antioxidants to alleviate disease severity. We used two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the impact of the thiol antioxidant, N-acetylcysteine (NAC), on protein expression in a murine OVA model. At least six proteins or protein families were found to be significantly increased in BALF from OVA-challenged mice compared to a control group: chitinase 3-like protein 3 (Ym1), chitinase 3-like protein 4 (Ym2), acidic mammalian chitinase (AMCase), pulmonary surfactant-associated protein D (SP-D), resistin-like molecule α (RELMα) or “found in inflammatory 1” (FIZZ1), and haptoglobin α-subunit. A total of 9 proteins were significantly increased in lung tissue from the murine asthma model, including Ym1, Ym2, FIZZ1, and other lung remodeling-related proteins. Western blotting confirmed increased Ym1/Ym2, SP-D, and FIZZ1 expression measured from BAL fluid and lung tissue from OVA-challenged mice. Intraperitoneal NAC administration prior to the final OVA challenge inhibited Ym1/Ym2, SP-D, and FIZZ1 expression in BALF and lung tissue. The oxidative stress proteins, Ym1/Ym2, FIZZ1 and SP-D, could play an important role in the pathogenesis of asthma and may be useful oxidative stress markers.