[IL-27 regulates the expression of Mac-1, fMLP-R and IL-1beta in human neutrophils through p38 MAPK and PI3K signal pathways].
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.
Li
Jian-Ping
JP
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.
Yang
Shao-Guang
SG
Dong
Chun-Lan
CL
Wu
Hao
H
Jia
Hai-Rong
HR
Zhao
Yan-Jin
YJ
Wang
Tong
T
Lu
Shi-Hong
SH
Ren
Qian
Q
Zhao
Qin-Jun
QJ
Xing
Wen
W
Zhang
Lei
L
Han
Zhong-Chao
ZC
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*
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