IL-27 regulates the expression of Mac-1, fMLP-R and IL-1beta in human neutrophils through p38 MAPK and PI3K signal pathways.
- Author:
Jian-Ping LI
1
;
Shao-Guang YANG
;
Chun-Lan DONG
;
Hao WU
;
Hai-Rong JIA
;
Yan-Jin ZHAO
;
Tong WANG
;
Shi-Hong LU
;
Qian REN
;
Qin-Jun ZHAO
;
Wen XING
;
Lei ZHANG
;
Zhong-Chao HAN
Author Information
1. 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.
- Publication Type:Journal Article
- MeSH:
Butadienes;
pharmacology;
Chromones;
pharmacology;
Down-Regulation;
Humans;
Imidazoles;
pharmacology;
Interleukin-1beta;
metabolism;
Interleukins;
metabolism;
Macrophage-1 Antigen;
metabolism;
Morpholines;
pharmacology;
Neutrophils;
metabolism;
Nitriles;
pharmacology;
Phosphatidylinositol 3-Kinases;
metabolism;
Pyridines;
pharmacology;
Receptors, Formyl Peptide;
metabolism;
Signal Transduction;
Up-Regulation;
p38 Mitogen-Activated Protein Kinases;
metabolism
- From:
Journal of Experimental Hematology
2010;18(2):391-395
- CountryChina
- Language:Chinese
-
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.
