Relationships between glutaredoxin 1 and cytokine levels in a murine model of allergic airway inflammation

Background: Glutaredoxin 1 (Glrx1) catalyzes a reduction of S-glutathionylated protein (PrSSG) and its expression increases in the murine lungs of allergic airway inflammation and in sputum of patients with asthma. Glrx1 also regulates a production of inflammatory mediators. We hypothesized that Glrx1 would synergistically induce an inflammatory response along with Th2 and NF-κB related cytokines in a murine model of allergic airway inflammation. Aims: To show relationships between Glrx1, and Th2 or NF-κB related cytokine levels as well as the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). Methods: BALB/c mice received three aerosol challenges with ovalbumin (OVA) or PBS following sensitization to OVA, then were sacrificed at 6, 24, 48, or 72 h, or 8 days. Th2 or NF-κB related cytokine levels in BALF were assessed using a Procarta Immnoassay kit. Results: Th2-related eotaxin at 6 and 48 h, IL-4 at 6 h, IL-5 at 6 and 24 h, and TGF-β at 6 h to 8 days after final challenge were significantly increased compared to controls in BALF (p<0.05). Levels of eotaxin, IL-4, IL-5, KC, TNF-α, and MCP-1 as well as the number of neutrophils in BALF were significantly correlated with Glrx1 in BALF, while TGF-β level and the number of eosinophils in BALF were significantly correlated with Glrx1 in the lung tissue (p<0.05). Conclusions: Our data identified a sequential production of Th2 and NF-κB related cytokines followed by TGF-β in a murine model of allergic airway inflammation, which was differentially associated with Glrx1 levels in BALF and the lung tissue.