N-(coumarin-3-yl)cinnamamide Promotes Immunomodulatory, Neuroprotective, and Lung Function-Preserving Effects during Severe Malaria.

Plasmodium berghei ANKA (PbA) infection in mice resembles several aspects of severe malaria in humans, such as cerebral malaria and acute respiratory distress syndrome. Herein, the effects of N-(coumarin-3-yl)cinnamamide (M220) against severe experimental malaria have been investigated. Treatment with M220 proved to protect cognitive abilities and lung function in PbA-infected mice, observed by an object recognition test and spirometry, respectively. In addition, treated mice demonstrated decreased levels of brain and lung inflammation. The production and accumulation of microglia, and immune cells that produce the inflammatory cytokines TNF and IFN-γ, decreased, while the production of the anti-inflammatory cytokine IL-10 by innate and adaptive immune cells was enhanced. Treatment with M220 promotes immunomodulatory, neuroprotective, and lung function-preserving effects during experimental severe malaria. Therefore, it may be an interesting therapeutic candidate to treat severe malaria effects.

Role of Suppressor of cytokine signaling 2 during the development and resolution of an experimental arthritis.

Rheumatoid arthritis(RA) is a debilitating chronic inflammatory disease. Suppressors of Cytokine Signaling(SOCS) proteins regulate homeostasis and pathogenesis in several diseases. The intersection between RA pathophysiology and SOCS2 is unclear. Herein, we investigated the roles of SOCS2 during the development of an experimental antigen-induced arthritis(AIA). In wild type mice, joint SOCS2 expression was reduced during AIA development. At the peak of inflammation, SOCS2-/- mice presented with reduced numbers of infiltrated cells in their joints. At the late phase of AIA, however, exhibited increased adhesion/infiltration of neutrophils, macrophages, CD4+-T cells, CD4+CD8+-T cells, and CD4-CD8--T cells associated with elevated IL-17 and IFN-γ levels, joint damage, proteoglycan loss, and nociception. SOCS2 deficiency resulted in lower numbers of apoptotic neutrophils and reduced efferocytosis. The present study demonstrated the vital role of SOCS2 during the development and resolution of an experimental RA model. Hence, this protein may be a novel therapeutic target for this disorder.

SOCS2 expression in hematopoietic and non-hematopoietic cells during Trypanosoma cruzi infection: Correlation with immune response and cardiac dysfunction.

Chagas disease has a complex pathogenesis wherein the host immune response is essential for controlling its development. Suppressor of cytokine signaling(SOCS)2 is a crucial protein that regulates cytokine production. In this study, SOCS2 deficiency resulted in an initial imbalance of IL12- and IL-10-producing neutrophils and dendritic cells (DCs), which caused a long-lasting impact reducing inflammatory neutrophils and DCs, and tolerogenic DCs at the peak of acute disease. A reduced number of inflammatory and pro-resolving macrophages, and IL17A-producing CD4+ T cells, and increased lymphocyte apoptosis was found in SOCS2-deficient mice. Electrocardiogram analysis of chimeric mice showed that WT mice that received SOCS2 KO bone marrow transplantation presented increased heart dysfunction. Taken together, the results demonstrated that SOCS2 is a crucial regulator of the immune response during Trypanosoma cruzi infection, and suggest that a SOCS2 genetic polymorphism, or failure of its expression, may increase the susceptibility of cardiomyopathy development in Chagasic patients.