rs-504393 and Asthma

Interleukin (IL)-17 has been implicated in the pathogenesis of asthma and the progression of airway inflammation. Here, we used a model of allergic asthma and found that the frequencies of IL-17-secreting T helper (Th)17 and CD8 (Tc)17 cells were both significantly increased, as was the expression of the CC chemokine receptor (CCR2) on the surface of these cells. CC chemokine ligand 2 (CCL2) has been shown to mediate the activation and recruitment of inflammatory cells in asthma, which are also skewed after ovalbumin (OVA) challenge. However, the role of CCL2 on Th17 cells and Tc17 cells in asthma has not been illuminated.. Mice that were sensitized and challenged with OVA received anti-CCL2 antibody (Ab; 5 μg/day intratracheally) or CCR2 antagonist (RS504393, 2 mg/kg/day intraperitoneally) prior to the challenge. Some mice received an isotype control Ab or vehicle alone. We then assessed the effects of allergic asthma and anti-CCL2 Ab or CCR2 antagonist treatment on the levels of IL-17 and CCL2, the Th17 and Tc17 cell frequencies and lung tissue inflammation.. We demonstrated that CCL2 and IL-17 levels and the frequency of Th17 and Tc17 cells in lung tissues and bronchoalveolar lavage fluid increased in the asthma group compared with the normal control mice. Blocking the CCL2/CCR2 axis greatly reduced the Th17 but not the Tc17 cell frequency, and revealed a suppressive effect on airway inflammation.. These findings indicate a role for the CCL2/CCR2 axis in mediating Th17 but not Tc17 cell migration during acute allergic airway inflammation.

Topics: Animals; Antibodies, Neutralizing; Asthma; Benzoxazines; Bronchoalveolar Lavage Fluid; CD8-Positive T-Lymphocytes; Chemokine CCL2; Disease Models, Animal; Female; Gene Expression; Humans; Interleukin-17; Lung; Lymphocyte Count; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors, CCR2; Spiro Compounds; Th17 Cells