title: Anti-inflammatory effects of propofol are mediated by apolipoprotein M in a hepatocyte nuclear factor-1α-dependent manner.
abstract: Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous hypnotic agent in daily practice. However, its anti-inflammatory properties have seldom been addressed. In this study, we evaluated the anti-inflammatory activity and mechanisms of propofol on lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro and found that propofol markedly inhibited LPS-induced production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and expression of inducible nitric oxide synthase (iNOS). At the same time, the expression of hepatocyte nuclear factor-1α (HNF-1α) and apolipoprotein M (APOM) was inhibited by treatment with LPS and LPS-induced down-regulation of HNF-1α expression and APOM expression could be compensated by propofol treatment. However, propofol could not compensate LPS-induced down-regulation of APOM expression by treatment with HNF-1α siRNA and the suppressive effect on LPS-induced pro-inflammatory cytokines production by propofol was significantly compensated by treatment with APOM siRNA. These results provide evidence that propofol may first up-regulate APOM expression by enhancing HNF-1α expression and then inhibit pro-inflammatory cytokine production in LPS-stimulated cells. Therefore, our study may be useful in understanding the critical effect of propofol in patients with systemic inflammatory response syndrome.
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Hu
authors.forename: Zhen-Long
authors.initials: ZL
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Qiu
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Huang
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Wu
authors.forename: Xin-Ru
authors.initials: XR
authors.lastname: Mao
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Zhao
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Li
authors.forename: Miao-Ning
authors.initials: MN
authors.lastname: Gu
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001053:Apolipoproteins / Q000378:metabolism*; D000075243:Apolipoproteins M; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D054834:Lipocalins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051839:NFI Transcription Factors / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*
chemical_list: C400523:APOM protein, human; D000894:Anti-Inflammatory Agents, Non-Steroidal; C501623:ApoM protein, mouse; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D051538:Hepatocyte Nuclear Factor 1-alpha; D054834:Lipocalins; D008070:Lipopolysaccharides; D051839:NFI Transcription Factors; D015742:Propofol