[Down-regulation of Toll-like receptor 4 is related to the tolerance to lipopolysaccharide in rat alveolar macrophages].
OBJECTIVE
To explore the change of expression of Toll-like receptor 4 (TLR(4)) related to the tolerance to lipopolysaccharide (LPS) in rat alveolar macrophages.


METHODS
Alveolar macrophages obtained from 30 Wistar male rats were randomly divided into a control group, a LPS single-dose stimulation group and a LPS double-dose stimulation group. IL-10 and IL-18 mRNA in alveolar macrophages and the level of TNF-alpha, as indexes of LPS tolerance, were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunoads orbeen assay (ELISA), respectively. The expression of TLR(4) was detected by Western Blot.


RESULTS
The level of TNF-alpha, and the mRNA for IL-10 and IL-18, and the protein of TLR(4) in the alveolar macrophages stimulated with single-dose LPS (100 ng/ml) were highly increased as compared with the control group [(0.760 +/- 0.030) micro g/L, 2.18 +/- 0.09, 1.83 +/- 0.07, 2.060 +/- 0.060, 148.3 +/- 1.4 vs (0.450 +/- 0.010) micro g/L, 1.16 +/- 0.04, 0.97 +/- 0.03, 1.320 +/- 0.020, 58.1 +/- 0.4 (P < 0.01)], while they were significantly decreased in the alveolar macrophages after re-stimulation with double-dose LPS (100 ng/ml and 500 ng/ml).


CONCLUSIONS
(1) The tolerance to LPS in alveolar macrophages can be induced by re-stimulation with LPS. (2) The down-regulated expression of TLR(4) is related to tolerance to LPS.
Zhang
De-ming
DM
Institute of Respiratory Diseases Research of PLA, Xinqiao Hospital, Chongqing 400037, China.
Li
Yong-wang
YW
Mao
Bao-ling
BL
Qian
Gui-sheng
GS
D000818:Animals; D015536:Down-Regulation; D016753:Interleukin-10 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D020382:Interleukin-18; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10