Brazilian Red Propolis Attenuates Inflammatory Signaling Cascade in LPS-Activated Macrophages

Autor(es)

Bueno-Silva, Bruno ^[1] ; Kawamoto, Dione ^[1] ; Ando-Suguimoto, Ellen S. ^[1] ; Alencar, Severino M. ^[2] ; Rosalen, Pedro L. ^[3] ; Mayer, Marcia P. A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, SP - Brazil

^[2] ESALQ USP, Coll Agr Luiz de Queiroz, Piracicaba, SP - Brazil

^[3] Univ Campinas UNICAMP, Dept Physiol Sci, Piracicaba Dent Sch, Piracicaba, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 12 DEC 14 2015.
• Citações Web of Science: 17

Resumo

Although previous studies suggested an anti-inflammatory property of Brazilian red propolis (BRP), the mechanisms involved in the anti-inflammatory effects of BRP and its activity on macrophages were still not elucidated. This study aimed to evaluate whether BRP attenuates the inflammatory effect of LPS on macrophages and to investigate its underlying mechanisms. BRP was added to RAW 264.7 murine macrophages after activation with LPS. NO production, cell viability, cytokines profile were evaluated. Activation of inflammatory signaling pathways and macrophage polarization were determined by RT-qPCR and Western blot. BRP at 50 mu g/ml inhibited NO production by 78% without affecting cell viability. Cd80 and Cd86 were upregulated whereas mrc1 was down regulated by BRP indicating macrophage polarization at M1. BRP attenuated the production of pro-inflammatory mediators IL-12, GM-CSF, IFN-gamma, IL-1 beta in cell supernatants although levels of TNF-alpha and IL-6 were slightly increased after BRP treatment. Levels of IL-4, IL-10 and TGF-beta were also reduced by BRP. BRP significantly reduced the up-regulation promoted by LPS of transcription of genes in inflammatory signaling (Pdk1, Pak1, Nfkb1, Mtcp1, Gsk3b, Fos and Elk1) and of Il1 beta and Il1f9 (fold-change rate >5), which were further confirmed by the inhibition of NF-kappa B and MAPK signaling pathways. Furthermore, the upstream adaptor MyD88 adaptor-like (Mal), also known as TIRAP, involved in TLR2 and TLR4 signaling, was down-regulated in BRP treated LPS-activated macrophages. Given that BRP inhibited multiple signaling pathways in macrophages involved in the inflammatory process activated by LPS, our data indicated that BRP is a noteworthy food-source for the discovery of new bioactive compounds and a potential candidate to attenuate exhacerbated inflammatory diseases. (AU)

• Processo FAPESP: 12/14323-3 - Avaliação dos efeitos da própolis vermelha e seus compostos bioativos na modulação da resposta de macrófagos
• Beneficiário: Marcia Pinto Alves Mayer
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/01500-4 - Avaliação dos efeitos da própolis vermelha e seus compostos bioativos na modulação da resposta de macrófagos
• Beneficiário: Bruno Bueno Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado