Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF-induced p47PHOX phosphorylation through a decrease in ERK1/2 activity

被引:58
作者
Dang, Pham My-Chan
Elbim, Carole
Marie, Jean-Claude
Chiandotto, Melanie
Gougerot-Pocidalo, Marie-Anne
El-Benna, Jamel
机构
[1] CHU Xavier Bichat, INSERM, U773, Fac Med, F-75018 Paris, France
[2] Univ Paris Denis Diderot 7, Paris, France
[3] AP HP, CIB, Paris, France
关键词
IL-10; NADPH oxidase; inflammation; ROS;
D O I
10.1096/fj.05-5395fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin-10 (IL-10) exerts its anti-inflammatory properties by down-regulating polymorphonuclear neutrophil (PMN) functions such as reactive oxygen species (ROS) production via NADPH oxidase. The molecular mechanisms underlying this process are unclear. Partial phosphorylation of the NADPH oxidase cytosolic component p47(PHOX) induced by proinflammatory cytokines, such as granulocyte-macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha, is essential for priming ROS production by PMN. The aim of this study was to determine whether IL-10 inhibits GM-CSF- and TNF alpha-induced p47PHOX phosphorylation and to investigate the molecular mechanisms involved in this effect. We found that IL-10 selectively inhibited GM-CSF- but not TNF alpha-induced p47PHOX phosphorylation in a concentration-dependent manner. As GM-CSF-induced p47(PHOX) phosphorylation is mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), we tested the effect of IL-10 on this pathway. We found that IL-10 inhibited GM-CSF-induced ERK1/2 activity in an immunocomplex kinase assay. This inhibitory effect was confirmed by analyzing the phosphorylation status of the endogenous substrate of ERK1/2, p90RSK, in intact PMN. Furthermore, IL-10 decreased ROS production by adherent GM-CSF-treated PMN in keeping with the higher ROS production observed in whole blood from IL-10 knockout mice compared to their wild-type counterparts. Together, these results suggest that IL-10 inhibits GM-CSF-induced priming of ROS production by inhibiting p47PHOX phosphorylation through a decrease in ERK1/2 activity. This IL-10 effect could contribute to the tight regulation of NADPH oxidase activity at the inflammatory site.
引用
收藏
页码:1504 / +
页数:12
相关论文
共 62 条
[1]   Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils - Selective activation of Jak2, Stat3, and Stat5B [J].
Al-Shami, A ;
Mahanna, W ;
Naccache, PH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (02) :1058-1063
[2]  
BABIOR BM, 1984, BLOOD, V64, P959
[3]   INVOLVEMENT OF PROTEIN-KINASE-C AND OF PROTEIN PHOSPHATASE-1 AND/OR PHOSPHATASE-2A IN P47 PHOX PHOSPHORYLATION IN FORMYLMET-LEU-PHE STIMULATED NEUTROPHILS - STUDIES WITH SELECTIVE INHIBITORS RO-31-8220 AND CALYCULIN-A [J].
BENGISGARBER, C ;
GRUENER, N .
CELLULAR SIGNALLING, 1995, 7 (07) :721-732
[4]  
BERKOW RL, 1987, J IMMUNOL, V139, P3783
[5]  
Bovolenta C, 1998, J IMMUNOL, V160, P911
[6]  
Brizzi MF, 1996, J BIOL CHEM, V271, P3562
[7]   Modulatory effect of interleukin-10 on the production of platelet-activating factor aod superoxide anions by human leucocytes [J].
Bussolati, B ;
Mariano, F ;
Montrucchio, G ;
Piccoli, G ;
Camussi, G .
IMMUNOLOGY, 1997, 90 (03) :440-447
[8]   Interleukin-10 down-regulates oxidative metabolism and antibody-dependent cellular cytotoxicity of human neutrophils [J].
Capsoni, F ;
Minonzio, F ;
Ongari, AM ;
Carbonelli, V ;
Galli, A ;
Zanussi, C .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1997, 45 (03) :269-275
[9]   INTERLEUKIN-10 (IL-10) INHIBITS THE RELEASE OF PROINFLAMMATORY CYTOKINES FROM HUMAN POLYMORPHONUCLEAR LEUKOCYTES - EVIDENCE FOR AN AUTOCRINE ROLE OF TUMOR-NECROSIS-FACTOR AND IL-1-BETA IN MEDIATING THE PRODUCTION OF IL-8 TRIGGERED BY LIPOPOLYSACCHARIDE [J].
CASSATELLA, MA ;
MEDA, L ;
BONORA, S ;
CESKA, M ;
CONSTANTIN, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (06) :2207-2211
[10]   INTERLEUKIN-10 (IL-10) UP-REGULATES IL-1 RECEPTOR ANTAGONIST PRODUCTION FROM LIPOPOLYSACCHARIDE-STIMULATED HUMAN POLYMORPHONUCLEAR LEUKOCYTES BY DELAYING MESSENGER-RNA DEGRADATION [J].
CASSATELLA, MA ;
MEDA, L ;
GASPERINI, S ;
CALZETTI, F ;
BONORA, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (05) :1695-1699