Toll-like receptor 4 siRNA attenuates LPS-induced secretion of inflammatory cytokines and chemokines by macrophages.
Toll-like receptor 4 (TLR4) is critical for activation of macrophages by Lipopolysaccharide (LPS). In this study, we investigated the silencing effects of TLR4-specific 21-nt small interfering RNAs (siRNA) on TLR4 expression in RAW264.7 cells. It was found that treatment with TLR4 siRNA down-regulated the TLR4 mRNA and protein expression in macrophage RAW264.7 cells, and reduced the sensitivity of the cells to LPS stimulation. Our findings also demonstrate that treatment with TLR4 siRNA significantly decreased the tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein 2 (MIP-2) expression induced by LPS. TLR4 siRNA treatment also impaired the signalling of mitogen-activated protein kinases (MAPK) induced by LPS in RAW264.7 cells. These data suggest that inhibition of TLR4 expression by TLR4 siRNA may be therapeutically beneficial in controlling the overall responses of immune cells to LPS.
Xu
Zhe
Z
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 1 XinYi Road, Ba Qiao District, Xi'an 710038, Shaanxi, PR China.
Huang
Chang-Xing
CX
Li
Yu
Y
Wang
Ping-Zhong
PZ
Ren
Guang-Li
GL
Chen
Chang-Sheng
CS
Shang
Fu-Jun
FJ
Zhang
Yan
Y
Liu
Qing-Quan
QQ
Jia
Zhan-Sheng
ZS
Nie
Qing-He
QH
Sun
Yong-Tao
YT
Bai
Xue-Fan
XF
D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D020868:Gene Silencing; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4