title: [IL-27 regulates the expression of Mac-1, fMLP-R and IL-1beta in human neutrophils through p38 MAPK and PI3K signal pathways].
abstract: The present study was aimed to investigate the pathways, by which IL-27 regulates the expression of adherent molecule Mac-1, chemotactic factor receptor fMLP-R and pro-inflammatory cytokine IL-1beta in human neutrophils. Highly purified human neutrophils were isolated from peripheral blood using Ficoll-Hypaque gradients centrifugation and erythrocyte lysis. The mRNA expression of IL-27 receptor components (WSX-1/TCCR and gp130) in human neutrophils was detected by reverse transcription polymerase chain reaction (RT-PCR). After incubation with IL-27 and specific inhibitors (p38 MAPK inhibitor SB203580, PI3K inhibitor LY294002 and ERK inhibitor U0126), the mRNA levels of fMLP-R and IL-1beta were determined by real time RT-PCR, and the adherent molecule Mac-1 expression in human neutrophils was determined by flow cytometry. The IL-1beta level in culture supernatant of human neutrophils was assayed by radioimmunoassay. The results showed that IL-27 receptor components (WSX-1/TCCR and gp130) were constitutively expressed in human neutrophils. IL-27 down-regulated Mac-1 expression in human neutrophils (p<0.05). After incubation with specific inhibitors, SB203580, not LY294002 and U0126, inhibited the down-regulation of Mac-1 expression by IL-27. However, IL-27 up-regulated the mRNA expression of fMLP-R and IL-1beta, and increased the release of IL-1beta (p<0.05). Interestingly, LY294002, not SB203580 and U0126, inhibited the up-regulation of fMLP-R and IL-1beta by IL-27. It is concluded that the IL-27 may regulate the expression of Mac-1, fMLP-R and IL-1beta in human neutrophils through p38 MAPK and PI3K signal pathways.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Li
authors.forename: Shao-Guang
authors.initials: SG
authors.lastname: Yang
authors.forename: Chun-Lan
authors.initials: CL
authors.lastname: Dong
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Jia
authors.forename: Yan-Jin
authors.initials: YJ
authors.lastname: Zhao
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Lu
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: Qin-Jun
authors.initials: QJ
authors.lastname: Zhao
authors.forename: Wen
authors.initials: W
authors.lastname: Xing
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhong-Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D002070:Butadienes; D002867:Chromones; D007093:Imidazoles; D053583:Interleukin-1beta; D007378:Interleukins; D016177:Macrophage-1 Antigen; D009025:Morpholines; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D011725:Pyridines; D044042:Receptors, Formyl Peptide; D048051:p38 Mitogen-Activated Protein Kinases; C464565:MYDGF protein, human; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093642:SB 203580