[Effect of diallyl trisulfide on tumor necrosis factor-alpha expression and nuclear factor-KappaB activity in mice with acute lung injury induced by lipopolysaccharide].
OBJECTIVE
To investigate the effect of diallyl trisulfide (DATS) on tumor necrosis factor-alpha (TNF-alpha) expression and nuclear factor-KappaB (NF-KappaB) activity in mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS).


METHODS
ALI murine model was reproduced by injection of LPS intraperitoneally. Mice were randomly divided into normal saline control group, ALI group, DATS prevention group, DATS treatment group, and DATS control group. The TNF-alpha levels in the serum and in the supernatant of lung homogenates were measured with enzyme linked immunoadsorbent assay (ELISA). The expression of TNF-alpha mRNA in the lung tissues was detected by reverse transcription polymerase chain reaction (RT-PCR). NF-KappaB activity in the lung tissues was detected by electrophoresis mobility shift assay (EMSA).


RESULTS
The levels of TNF-alpha induced by LPS in the serum and the supernatant of lung homogenates were increased markedly at 2 hours in ALI group (both P<0.01), and decreased at 6 hours, but they were still higher than those of the control groups (all P<0.01). They were reduced in DATS prevention group at 2 and 6 hours compared with those of ALI group (P<0.05 or P<0.01), but no change was noted in DATS treatment group (all P>0.05). The expression of TNF-alpha mRNA in the lung tissues of ALI group increased markedly at 2 hours compared with those of control groups (both P<0.01), and it could be down-regulated by pretreatment with DATS (P<0.05). No change in DATS was found in treatment group. NF-KappaB activity in the lung tissue increased in ALI group compared with that of control groups (both P<0.05), and it was markedly reduced in DATS prevention group (P<0.05), but no change was found in DATS treatment group.


CONCLUSIONS
Pretreatment of DATS for ALI in mice could inhibit NF-KappaB activity, TNF-alpha mRNA expression in lung tissues, and decrease the release of TNF-alpha in the serum and the lung homogenates, and they might be the underlying mechanisms of prevention of the occurrence of ALI by DATS.
Zhu
Gui-Jun
GJ
The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. guijun10@sina.com
Liu
Jun-Feng
JF
Yu
Zhan-Biao
ZB
Zhang
Yu-Xiang
YX
Hu
Zhen-Jie
ZJ
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013440:Sulfides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000498:Allyl Compounds; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; C042577:diallyl trisulfide