[Effects of artesunate on CD14 and toll-like receptor 4 in peritoneal macrophages of mice with heat stroke endotoxemia].
OBJECTIVE
To study the effects of artesunate on CD14 and toll-like receptor 4 (TLR 4) expressions in peritoneal macrophages of mice with heat stroke endotoxemia.


METHODS
Kunming mice were randomly divided into the normal temperature group, the hyperthermia group, the normal saline (NS) group and the artesunate group (both i.p.60 mg/kg daily for consecutive five days). The normal temperature group was exposed to the condition of dry bulb temperature (Tdb) 25 degrees C +/- 0.5 degrees C and relative humidity (RH) 43% +/- 5% for 2 hours, while other groups were exposed to the condition of Tdb 35 degrees C +/- 0.5 degrees C and RH 65% +/- 5%. The mRNA expressions of CD14 and TLR 4 in peritoneal macrophages and concentrations of tumor necrosis factor alpha (TNF alpha) in plasma were observed in different time points (1 hour and 2 hour).


RESULTS
The mRNA expressions of CD14 and TLR 4 in the normal temperature group were 0.34% +/- 0.047% and 0.31% +/- 0.062% respectively. The expressions of two receptors at 1 hour in the hyperthermia group were significantly increased to 0.53% +/- 0.085% and 0.45% +/- 0.049% compared with the normal group and kept increased at 2 hour (P < 0.01). The mRNA expressions at 1 hour in the NS group were significantly increased but a little bit decreased at 2 hour. The mRNA expressions of CD14 and TLR 4 at 1 hour in the artesunate group were 0.26% +/- 0.051% and 0.25% +/- 0.084% respectively and a little bit decreased at 2 hour. The change of TNF-alpha in each group was almost consistent with the changes of CD14 and TLR 4.


CONCLUSIONS
Artesunate can reduce significantly the expressions of CD14 and TLR 4 in LPS signal transduction pathway and the concentration of TNF-alpha, which perhaps is one of the most important mechanisms that artesunate fights against endotoxemia.
Zhang
Pei
P
Department of Thermal Environment Medicine, Nan Fang Medical University, Guangzhou 510515, China.
Chen
Xue-mei
XM
Luo
Bing-de
BD
Tan
Qing
Q
Zou
Fei
F
Wan
Wei-ren
WR
Guo
Jin-qiang
JQ
D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002478:Cells, Cultured; D019446:Endotoxemia / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018883:Heat Stroke / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics
D037621:Artemisinins; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D012717:Sesquiterpenes; D051197:Toll-Like Receptor 4; D000077332:Artesunate