Navegando por Autor "Birbrair, Alexander"
Agora exibindo 1 - 2 de 2
Resultados por página
Opções de Ordenação
Item High-density-immune-complex regulatory macrophages promote recovery of experimental colitis in mice.(2021) Lopes, Tamara Cristina Moreira; Almeida, Gregório Guilherme; Souza, Izabela Aparecida; Borges, Diego Costa; Lima, Wanderson Geraldo de; Prazeres, Pedro Henrique Dias Moura; Birbrair, Alexander; Arantes, Rosa Maria Esteves; Mosser, David M.; Gonçalves, RicardoMacrophages not only play a fundamental role in the pathogenesis of inflam- matory bowel disease (IBD), but they also play a major role in preserving intestinal homeo- stasis. In this work, we evaluated the role of macrophages in IBD and investigated whether the functional reprogramming of macrophages to a very specific phenotype could decrease dis- ease pathogenesis. Thus, macrophages were stimulated in the presence of high-density immune complexes which strongly upregulate their production of IL-10 and downregulate pro-inflammatory cytokines. The transfer of these high-density-immune-complex regulatory macrophages into mice with colitis was examined as a potential therapy proposal to control the disease. Animals subjected to colitis induction received these high-density-immune- complex regulatory macrophages, and then the Disease Activity Index (DAI), and macro- scopic and microscopic lesions were measured. The treated group showed a dramatic improvement in all parameters analyzed, with no difference with the control group. The colon was macroscopically normal in appearance and size, and microscopically colon architecture was preserved. The immunofluorescence migration assay showed that these cells migrated to the inflamed intestine, being able to locally produce the cytokine IL-10, which could explain the dramatic improvement in the clinical and pathological condition of the animals. Thus, our results demonstrate that the polarization of macrophages to a high IL-10 producer profile after stimulation with high-density immune complexes was decisive in controlling experimental colitis, and that macrophages are a potential therapeutic target to be explored in the control of colitis.Item Inhalation of dimethyl fumarate-encapsulated solid lipid nanoparticles attenuate clinical signs of experimental autoimmune encephalomyelitis and pulmonary inflammatory dysfunction in mice.(2022) Pinto, Bárbara Fernandes; Ribeiro, Lorena Natasha Brito; Silva, Gisela Bevilacqua Rolfsen Ferreira da; Freitas, Camila Simões de; Rocha, Lucas Kraemer; Oliveira, Fabrício Marcus Silva; Clímaco, Marianna Carvalho; Mourão, Flavio Afonso Gonçalves; Santos, Gabryella Soares Pinheiro dos; Béla, Samantha Ribeiro; Gurgel, Isabella Luísa da Silva; Leite, Fábio de Lima; Oliveira, Anselmo Gomes de; Vilela, Maura Regina Silva da Páscoa; Lima, Onésia Cristina Oliveira; Soriani, Frederico Marianetti; Fujiwara, Ricardo Toshio; Birbrair, Alexander; Russo, Remo de Castro; Tavares, Juliana CarvalhoRationale: The FDA-approved Dimethyl Fumarate (DMF) as an oral drug for Multiple Sclerosis (MS) treatment based on its immunomodulatory activities. However, it also caused severe adverse effects mainly related to the gastrointestinal system. Objective: Investigated the potential effects of solid lipid nanoparticles (SLNs) containing DMF, administered by inhalation on the clinical signs, central nervous system (CNS) inflammatory response, and lung function changes in mice with experimental autoimmune encephalomyelitis (EAE). Materials and methods: EAE was induced using MOG35–55 peptide in female C57BL/6J mice and the mice were treated via inhalation with DMF-encapsulated SLN (CTRL/SLN/DMF and EAE/SLN/DMF), empty SLN (CTRL/SLN and EAE/SLN), or saline solution (CTRL/saline and EAE/saline), every 72 h during 21 days. Results: After 21 days post-induction, EAE mice treated with DMF-loaded SLN, when compared with EAE/saline and EAE/SLN, showed decreased clinical score and weight loss, reduction in brain and spinal cord injury and inflammation, also related to the increased influx of Foxp3+ cells into the spinal cord and lung tissues. Moreover, our data revealed that EAE mice showed signs of respiratory disease, marked by increased vascular permeability, leukocyte influx, production of TNF-α and IL-17, perivascular and peribronchial inflammation, with pulmonary mechanical dysfunction associated with loss of respiratory volumes and elasticity, which DMF-encapsulated reverted in SLN nebulization. Conclusion: Our study suggests that inhalation of DMF-encapsulated SLN is an effective therapeutic protocol that reduces not only the CNS inflammatory process and disability progression, characteristic of EAE disease, but also protects mice from lung inflammation and pulmonary dysfunction.