title: Role of interplay between IL-4 and IFN-γ in the in regulating M1 macrophage polarization induced by Nattectin.
abstract: 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-γ), 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-γ cytokines. Furthermore, the induction of IL-6 release is negatively regulated by IL-4 and positively regulated by IL-12 and IFN-γ. 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.
authors.affiliation: Immunoregulation Unit, Special Laboratory of Applied Toxinology, Instituto Butantan, São Paulo, Brazil.
authors.forename: Edson Kiyotaka
authors.initials: EK
authors.lastname: Ishizuka
authors.forename: Marcio José
authors.initials: MJ
authors.lastname: Ferreira
authors.forename: Lidiane Zito
authors.initials: LZ
authors.lastname: Grund
authors.forename: Erica Maria Martins
authors.initials: EM
authors.lastname: Coutinho
authors.forename: Evilin Naname
authors.initials: EN
authors.lastname: Komegae
authors.forename: Alexandra Anjos
authors.initials: AA
authors.lastname: Cassado
authors.forename: Karina Ramalho
authors.initials: KR
authors.lastname: Bortoluci
authors.forename: Monica
authors.initials: M
authors.lastname: Lopes-Ferreira
authors.forename: Carla
authors.initials: C
authors.lastname: Lima
mesh_terms: D000818:Animals; D024541:Batrachoidiformes / Q000502:physiology*; D001854:Bone Marrow Cells / Q000187:drug effects; D005260:Female; D005397:Fish Venoms / Q000737:chemistry* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D005397:Fish Venoms; C556062:IL10 protein, mouse; D018793:Interleukin-13; D037181:Lectins, C-Type; C581368:nattectin protein, Thalassophryne nattereri; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma