Anti-inflammatory response in atherosclerosis: identification and characterization of the efect of IL-27 and IL-37

Author(s)

Liana Maria Villarejos

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2016-08-29

Examining board members

Maria Heloisa de Souza Lima Blotta; Marisa Passarelli; Carla Fernanda Franco Penteado

• Advisor: Maria Heloisa de Souza Lima Blotta; Rômulo Tadeu Dias de Oliveira

Abstract

Atherosclerosis is caused by the accumulation of cholesterol in the intima of the arteries, leading to the infiltration of inflammatory cells. The balance between inflammatory and anti-inflammatory response at these sites is crucial for the development of atherosclerotic plaques and disease progression. Several studies have described the important role of anti-atherogenic cytokines such as IL-10 and TGF-? in atherosclerosis control. Recently, IL-27 and IL-37 have received attention due to their anti-inflammatory potential in inflammatory and autoimmune diseases. IL-27 belongs to the IL-12 family cytokines and is composed of two subunits EBI-3, and p28. IL-27 is the main inducer of the differentiation IL-10 producing Tr1 cells, besides being able to suppress the polarization of inflammatory cells, such as Th17 cells. On the other hand, IL-37 belongs to the IL-1 family cytokine and has 5 isoforms (a - e). Although it was expressed in low concentrations in monocytes and DCs, IL-37 is up regulated in the inflammatory context, where inhibits the production of inflammatory cytokines. This study aimed to verify the involvement of IL-27 and IL-37 in human atherosclerosis. First, we detected IL-27 and IL-37 in atherosclerotic lesions in patients undergoing carotid endarterectomy by immunohistochemistry. Both cytokines were detected in macrophages and giant cells in close contact with cholesterol crystals. Next, we evaluated the presence of these cytokines (mRNA and protein) in the peripheral blood of patients with chronic (SCC) and acute (SCA) coronary artery disease and controls with (FR) and without (C) risk factors for atherosclerosis. The expression of EBI-3 (IL-27 component) mRNA and plasma concentration of IL-27 was significantly lower in patients with SCC and SCA and FR individuals than in risk-factor control. These results suggest less control of the inflammatory response in the SCC groups, SCA and FR. Then we verify whether macrophages (M1 and M2) derived from peripheral blood monocytes are able to produce IL-27 and IL-37 in vitro after stimulation with atherogenic antigens. We observed a significant increase in IL-27 production, especially by M2 macrophages (inflammatory) when stimulated with LPS and oxLDL. Finally, we found that both IL-27 and IL-37 have strong inhibitory activity on the production of matrix metalloproteinases, cathepsin and chemokines by endothelial and smooth muscle cells. Taken together, our results showed that IL-27 and IL-37 exhibit anti-inflammatory potential, more pronounced for IL-27, which could represent an important control mechanism of the inflammatory response in atherosclerosis and in maintenance of homeostasis (AU)

• FAPESP's process: 13/26808-4 - Anti-inflammatory response in atherosclerosis: identification and characterization of cytokines IL-27 and IL-37
• Grantee: Liana Maria Villarejos
• Support Opportunities: Scholarships in Brazil - Master