El Chartouni, Carol and Rehli, Michael (2010) Comprehensive analysis of TLR4-induced transcriptional responses in interleukin 4-primed mouse macrophages. IMMUNOBIOLOGY, 215 (9-10). pp. 780-787. ISSN 0171-2985,
Full text not available from this repository. (Request a copy)Abstract
Interferon (IFN)gamma and interleukin (IL)-4 are central regulators of T helper 1 (Th1) and T helper 2 (Th2) immune responses, respectively. Both cytokines have a major impact on macrophage phenotypes: IFN gamma-priming and subsequent TLR4 activation induces so-called "classically activated" macrophages that are characterized by pronounced pro-inflammatory responses, whereas IL-4-treated macrophages, commonly called "alternatively activated", are known to develop enhanced capacity for endocytosis, antigen presentation and tissue repair and are generally considered anti-inflammatory. Considering IL-4 as priming rather than activating stimulus, we now compared the TLR4-dependent global gene activation program in IFN gamma- versus IL-4-pretreated mouse macrophages, which has rarely been studied so far. Although both cytokines frequently induced opposing effects on gene transcription, the subsequent activation of bone marrow-derived macrophages by lipopolysaccharide (LPS) produced a strong, priming-dependent pro-inflammatory response in both macrophage types. For example, the production of key pro-inflammatory cytokines IL-6 and IL-12 was significantly higher in IL-4- versus IFN gamma-primed macrophages and several cytokine genes, including 1119, Ccl17, Ccl22, Ccl24 and Cxcl5, were preferentially induced in "alternatively" primed and LPS activated mouse macrophages. In a subset of genes, including IL12a, IFN gamma-priming was actually found to suppress LPS-induced gene expression in a Stat1-dependent manner. Our data suggest that IL-4-priming is not per se anti-inflammatory but generates a macrophage that is "tissue protective" but still capable of mounting a strong inflammatory response after TLR4-dependent activation. (C) 2010 Elsevier GmbH. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LEISHMANIA-MAJOR AMASTIGOTES; ALTERNATIVE ACTIVATION; MURINE MACROPHAGES; INTERFERON-GAMMA; EXPRESSION; CYTOKINE; DIFFERENTIATION; HETEROGENEITY; MONOCYTE; RECEPTOR; Alternative macrophage activation; Gene regulation; Toll-like receptor |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2020 05:24 |
| Last Modified: | 15 Jul 2020 05:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24239 |
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