Toll-like receptor 4 relates to lipopolysaccharide-induced mucus hypersecretion in rat airway.
BACKGROUND
Toll-like receptor 4 (TLR4) is a transmembrane protein that participates in the recognition of lipopolysaccharide (LPS), a potentially important source of inflammation. To investigate the role of TLR4 in LPS-induced airway mucus hypersecretion (AMH), we used a LPS-induced rat model treated with dexamethasone (DEX).


METHODS
Rats were randomly divided into four experimental groups: 1) saline (SA)-treated with distilled water (DW) (control group); 2) LPS-treated with DW (LPS group); 3) LPS-treated with DEX (LPS plus DEX group); 4) SA-treated with DEX (DEX group). DEX (5 mg/kg) was intraperitoneally injected 1 h before being administered intratracheally with LPS. Expressions of TLR4 and MUC5AC were evaluated with RT-PCR, in situ hybridization, immunohistochemistry and Alcian blue/Periodic acid-schiff (AB/PAS) staining.


RESULTS
Increased expressions of TLR4 protein and mRNA were found in rat airway treated with LPS and peaked on day 2 after LPS administration. Following this, LPS increased MUC5AC expression and AB/PAS-stained goblet cells in rat airway. Correlation analysis showed TLR4 correlated well with the expression of MUC5AC (r = 0.684, p <0.01) and AB/PAS-stained area (r = 0.781, p <0.01). In addition, DEX pretreatment significantly reduced LPS-induced overexpression of TLR4 (p <0.05) in rat airway.


CONCLUSIONS
These results suggest TLR4 relates to LPS-induced AMH and support a role of TLR4 in DEX inhibition of LPS-induced AMH.
Chen
Lei
L
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, Sichuan University, Chengdu, Sichuan, China.
Wang
Tao
T
Zhang
Jian-Yong
JY
Zhang
Shang-Fu
SF
Liu
Dai-Shun
DS
Xu
Dan
D
Wang
Xun
X
Chen
Ya-Juan
YJ
Wen
Fu-Qiang
FQ
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009093:Mucus / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D003907:Dexamethasone