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 colitis mouse models. 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 asthma model. 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 of mouse TSLP, high mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) in airway epithelium and whole lung tissues were markedly increased in TDI group compared with control mice, which were decreased after administration of short TSLP. Meanwhile, short TSLP also inhibited STAT5(Y694) phosphorylation, which was highly expressed in airways of TDI-exposure mice. In vitro, both TDI-human serum albumin (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 asthma model, which might be associated with the inhibitions of HMGB1-RAGE and long TSLP expression and STAT5(Y694) phosphorylation.

• Authors: Yanhong Wang, Yanqing Le, Wenqu Zhao, Yun Lin, Yue Wu, Changhui Yu, Jing Xiong, Fei Zou, Hangming Dong, Shaoxi Cai, Haijin Zhao
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 157 Issue 2 Pg. 276-290 (06 01 2017) ISSN: 1096-0929 [Electronic] United States
• PMID: 28329851 (Publication Type: Journal Article)
• Copyright: © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Cytokines
• Glycation End Products, Advanced
• HMGB1 Protein
• Peptides
• Receptor for Advanced Glycation End Products
• STAT5 Transcription Factor
• Toluene 2,4-Diisocyanate
• Thymic Stromal Lymphopoietin

Topics

• Animals
• Asthma (chemically induced, drug therapy, immunology)
• Cell Line
• Cytokines (chemistry, genetics, therapeutic use)
• Disease Models, Animal
• Gene Expression (drug effects)
• Glycation End Products, Advanced (metabolism)
• HMGB1 Protein (antagonists & inhibitors, genetics)
• Humans
• Male
• Mice, Inbred BALB C
• Peptides (administration & dosage, chemistry, therapeutic use)
• Phosphorylation
• Protein Conformation
• Receptor for Advanced Glycation End Products (antagonists & inhibitors, genetics)
• STAT5 Transcription Factor (metabolism)
• Toluene 2,4-Diisocyanate (toxicity)
• Thymic Stromal Lymphopoietin