title: Toll-like receptor 4 siRNA attenuates LPS-induced secretion of inflammatory cytokines and chemokines by macrophages.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 1 XinYi Road, Ba Qiao District, Xi'an 710038, Shaanxi, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xu
authors.forename: Chang-Xing
authors.initials: CX
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Ping-Zhong
authors.initials: PZ
authors.lastname: Wang
authors.forename: Guang-Li
authors.initials: GL
authors.lastname: Ren
authors.forename: Chang-Sheng
authors.initials: CS
authors.lastname: Chen
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Shang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Liu
authors.forename: Zhan-Sheng
authors.initials: ZS
authors.lastname: Jia
authors.forename: Qing-He
authors.initials: QH
authors.lastname: Nie
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Sun
authors.forename: Xue-Fan
authors.initials: XF
authors.lastname: Bai
mesh_terms: 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
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4