Role of interplay between IL-4 and IFN-γ in the in regulating M1 macrophage polarization induced by Nattectin

被引:41
|
作者
Ishizuka, Edson Kiyotaka [1 ]
Ferreira, Marcio Jose [1 ]
Grund, Lidiane Zito [1 ]
Martins Coutinho, Erica Maria [1 ]
Komegae, Evilin Naname [1 ]
Cassado, Alexandra Anjos [2 ]
Bortoluci, Karina Ramalho [2 ]
Lopes-Ferreira, Monica [1 ]
Lima, Carla [1 ]
机构
[1] Inst Butantan, Unidade Imunorregulacao, Lab Especial Toxinol Aplicada, BR-05503900 Sao Paulo, Brazil
[2] Univ Fed Sao Paulo, Mol Immunol Innate Recognit Unit, Dept Biol Sci, Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
Nattectin; C-type lectin; M1; activation; Macrophages; Th1/Th2; cytokines; NATTERERI FISH VENOM; DENDRITIC CELLS; ALTERNATIVE ACTIVATION; KININOGENASE ACTIVITY; INTERFERON-GAMMA; IN-VITRO; T-CELLS; THALASSOPHRYNE; INTERLEUKIN-6; MODEL;
D O I
10.1016/j.intimp.2012.08.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recently our group described that Nattectin, a C-type lectin of the venom of Thalassophryne nattereri shows a potent pro-inflammatory capacity. Here, we demonstrated that Nattectin is able to induce M1 macrophage marker iNOS, and up-regulate the expression of MHC class II, CD80, CD86 and CD40 molecules. The increase in MHC class II and CD49a integrin expression with MMP-9 production and endocytic capacity depend on lectin function of Nattectin. Moreover, the polarization of peritoneal and bone marrow-derived macrophages induced by Nattectin to M1 profile is dependent on Th1 cytokines (IL-12 and IFN-gamma), and negatively regulated by Th2 cytokines (IL-4, IL-10 and IL-13). Also we reveal that IL-4 play a dual role in this polarization: a regular action of IL-4 was seen in the negative regulation of the CD40 expression, but an unexpected positive regulation was seen in the expression of CCR7 and MHC class II. Finally, our in vivo studies showed that the influx of neutrophils and small peritoneal macrophage - F4/80(low)MHCII(hi) induced by Nattectin is totally dependent on IL-4 and IFN-gamma cytokines. Furthermore, the induction of IL-6 release is negatively regulated by IL-4 and positively regulated by IL-12 and IFN-gamma. Together, the results allowed us to expand the knowledge about the regulation of macrophage activation, as well as confirmed the ability of Nattectin, a fish C-type lectin, as an important immunomodulatory agent. (c) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:513 / 522
页数:10
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