Blockage of thymic stromal lymphopoietin signaling improves acute lung injury in mice by regulating pulmonary dendritic cells

Objectives: To investigate the effects of blockage of thymic stromal lymphopoietin(TSLP) signaling by TSLP receptor (TSLPR)-immunoglobulin ( Ig) on acute lung injury (ALI) induced by lipopolysaccharide (LPS). Methods: C57BL/6 mice received TSLPR- Igor controlled- Igbefore being induced ALI. Lung wet/dry (W/D) weight ratio was recorded. Neutrophil number and albumin concentration of bronchoalveolar lavages fluids (BALF) were determined. Besides, bone marrow dendritic cells (BMDCs) were separated and cultured with medium, TSLP, TSLP plus TSLPR- Igor TSLP plus controlled- Ig. Protein expression levels of TSLP in lung tissues, phosphorylation extracellular regulated protein kinases (pERK) 1/2, p38, and signal transducers and activators of transcription (STAT) 3 in BMDCs were analyzed using Western blotting. Expression of CD40, CD80and CD86on pulmonary DCs and BMDCs was determined using flow cytometry (FCM). Results: The W/D ratio, neutrophil number and albumin concentration were significantly decreased in the TSLPR- Iggroup compared with the controlled- Igand model group. Moreover, there was a noticeable decrease in CD40, CD80or CD86expression by TSLPR- Igon both pulmonary DCs and BMDCs. The protein levels of TSLP, pERK1 and STAT3 were significantly decreased by TSLPR- Ig. However, no significant differences were found in p38 and pERK2. Conclusion: These results suggest that TSLP may be involved in ALI, and blockage of TSLP signaling using TSLPR- Igimproves ALI at least in part by regulation of DCs functions. The underling downstream signaling mediated by TSLP might be associated with activating the ERK1 and STAT3 signaling pathway.