AT-RvD1 modulates the activation of bronchial epithelial cells induced by lipopolysaccharide and Dermatophagoides pteronyssinus.

Bronchial epithelial cells are essential to airways homeostasis; however, they are also involved in exacerbation of airway inflammatory responses of patients with conditions such as asthma. Dermatophagoides pteronyssinus (Dp), the most important allergen, and lipopolysaccharide (LPS), both of which are present in house dust mites (HDM), can activate immune and structural cells (such as bronchial epithelial cells) and modulate the airway inflammation in asthma patients. Resolvin D1 (RvD1) and its epimer aspirin-triggered-resolvin D1 (AT-RvD1) are lipid mediators that are produced during the resolution of inflammation and demonstrate anti-inflammatory and pro-resolution effects in several experimental models including experimental models of allergic airway inflammation. Here, we evaluated the effects of AT-RvD1 (10(-12)-10(-10) M) on human bronchial epithelial cells (BEAS-2B) stimulated with LPS (2μg/ml) or Dp (10μg/ml). After 24h, the C-C motif chemokine ligand 2 (CCL-2) production was increased in cells that had been stimulated with LPS and Dp compared to the control. However, AT-RvD1 (10(-11) and 10(-10) M) significantly reduced the concentration of CCL-2 in a manner that was dependent on the N-formyl peptide receptor 2 (FPR2/ALX) and nuclear factor kappa B (NF-κB) pathways in cells stimulated with LPS or Dp compared to controls. In addition, AT-RvD1 reduced the phosphorylation of signal transducer and activator of transcription (STAT)6 and STAT1 in cells stimulated with Dp and LPS, respectively. In conclusion, AT-RvD1 demonstrated significant anti-inflammatory effects in bronchial epithelial cells that were stimulated with LPS or Dp, which provides new perspectives for therapeutic strategies to control inflammatory airway diseases.