Short thymic stromal lymphopoietin attenuates toluene diisocyanate-induced airway inflammation and inhibits high mobility group Box 1-receptor for advanced glycation end products and long thymic stromal lymphopoietin Expression

Abstract

Short thymic stromal lymphopoietin (short TSLP), one of TSLP variants, exerts anti-inflammatory activities in endotoxin shock and colitismousemodels. Our latest work reported that short TSLP prevented house dust mite-induced epithelial barrier disruption. Yet the role of short TSLP in toluene diisocyanate (TDI)-induced asthma is unknown. Male BALB/c mice were sensitized and challenged with TDI to generate a chemical-induced asthmamodel. Synthetic short TSLP peptides were given intranasally or intraperitoneally before each challenge. TDI significantly increased inflammation and hyperresponsiveness of airway, which were suppressed by short TSLP treatment. Levels ofmouse TSLP, high mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) in airway epitheliumand whole lung tissues were markedly increased in TDI group compared with controlmice, which were decreased after administration of short TSLP.Meanwhile, short TSLP also inhibited STAT5(Y694) phosphorylation, which was highly expressed in airways of TDI-exposuremice. In vitro, both TDI-human serumalbumin (HSA) and recombinant human (rh) HMGB1 promoted long TSLP but not short TSLP gene production in human bronchial epithelial cells (16HBE). Cells pre-treated with short TSLP exhibited less expression of RAGE and long TSLP and lower phosphorylation of Akt(S473), p38 MAPK(T180/Y182), and STAT5(Y694) than stimulated with TDI-HSA or rhHMGB1 alone. Results suggest that short TSLP prevents airway inflammation in a chemical-induced asthmamodel, which might be associated with the inhibitions of HMGB1-RAGE and long TSLP expression and STAT5(Y694) phosphorylation.