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.
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.
Authors: William D Bennett; Neil E Alexis; Martha Almond; Margaret Herbst; Kirby L Zeman; David B Peden Journal: J Aerosol Med Pulm Drug Deliv Date: 2014-12 Impact factor: 2.849
Authors: William D Bennett; Margaret Herbst; Kirby L Zeman; Jihong Wu; Michelle L Hernandez; David B Peden Journal: J Allergy Clin Immunol Date: 2012-10-25 Impact factor: 10.793