Anti-inflammatory properties of the PI3K pathway are mediated by IL-10/DUSP regulation

被引：53

作者：

Guenzl, Philipp ^{[1
]}

Bauer, Kathrin ^{[1
]}

Hainzl, Eva ^{[1
]}

Matt, Ulrich ^{[2
,3
]}

Dillinger, Barbara ^{[1
]}

Mahr, Benedikt ^{[1
]}

Knapp, Sylvia ^{[2
,3
]}

Binder, Bernd R. ^{[1
]}

Schabbauer, Gernot ^{[1
]}

机构：

[1] Med Univ Vienna, Ctr Biomol Med & Pharmacol, Dept Vasc Biol & Thrombosis Res, A-1090 Vienna, Austria

[2] Med Univ Vienna, Div Infect Dis & Trop Med, Dept Med 1, A-1090 Vienna, Austria

[3] Austrian Acad Sci CeMM, Res Ctr Mol Med, Vienna, Austria

来源：

JOURNAL OF LEUKOCYTE BIOLOGY | 2010年 / 88卷 / 06期

基金：

奥地利科学基金会;

关键词：

PTEN; inflammation; macrophage; INNATE IMMUNE-RESPONSES; MURINE PNEUMOCOCCAL PNEUMONIA; INFLAMMATORY RESPONSE; 3-KINASE PATHWAY; GENETIC-ANALYSIS; TISSUE FACTOR; EXPRESSION; PHOSPHATASE-1; CYTOKINE; RECEPTOR;

D O I：

10.1189/jlb.0110001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Resolution of inflammation is an important hallmark in the course of infectious diseases. Dysregulated inflammatory responses may have detrimental consequences for the affected organism. Therefore, tight regulation of inflammation is indispensable. Among numerous modulatory signaling pathways, the PI3K/PTEN signaling pathway has been proposed recently to be involved in the regulation of innate immune reactions. Here, we attempted to elucidate molecular mechanisms that contribute to the modulatory properties of the PI3K signaling pathway in inflammation. PTEN-deficient macrophages, which harbor constitutively active PI3Ks, were analyzed in response to gram-negative bacteria and PAMPs such as LPS. PTEN-deficient cells showed reduced inflammatory cytokine production, which was accompanied by reduced MAPK signaling activation in early-as well as late-phase activation. Simultaneously, we found increased levels of the MKP DUSP1, as well as the anti-inflammatory cytokine IL-10. Our data suggest that differential DUSP1 regulation coupled with enhanced IL-10 production contributes to the anti-inflammatory properties of the PI3K pathway. J. Leukoc. Biol. 88: 1259-1269; 2010.

引用

页码：1259 / 1269

页数：11

共 36 条

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