Liver X Receptor Activation Impairs Neutrophil Functions and Aggravates Sepsis

Autor(es)

Souto, Fabricio O. ^{[1, 2]} ; Castanheira, Fernanda V. S. ^{[3, 4]} ; Trevelin, Silvia C. ^{[3, 5]} ; Lima, Braulio H. F. ^[3] ; Martelossi Cebinelli, Guilherme Cesar ^[2] ; Turato, Walter M. ^[2] ; Auxiliadora-Martins, Maria ^[6] ; Basile-Filho, Anibal ^[6] ; Alves-Filho, Jose Carlos ^{[3, 4]} ; Cunha, Fernando Q. ^{[3, 4]}

Afiliação do(s) autor(es)

^[1] Univ Fed Pernambuco, Lab Immunopathol Keizo Asami, Recife, PE - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Ctr Res Inflammatory Dis, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[5] Kings Coll London, British Heart Fdn Ctr, Sch Cardiovasc Med & Sci, London - England

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol Surg & Anat, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Infectious Diseases; v. 221, n. 9, p. 1542-1553, MAY 1 2020.
• Citações Web of Science: 0

Resumo

Background. Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in several metabolic development and inflammatory disorders. Although neutrophils express both LXR-alpha and LXR-beta, the consequences of their activation, particularly during sepsis, remain unknown. Methods. We used the model of cecal ligation and puncture (CLP) to investigate the role of LXR activation during sepsis. Results. In this study, we verified that LXR activation reduces neutrophil chemotactic and killing abilities in vitro. Mice treated with LXR agonists showed higher sepsis-induced mortality, which could be associated with reduced neutrophil infiltration at the infectious foci, increased bacteremia, systemic inflammatory response, and multiorgan failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load, and multiorgan dysfunction. More important, neutrophils from septic patients showed increased ABCA1 messenger ribonucleic acid levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared with cells from healthy individuals. Conclusions. Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/03293-3 - Papel dos produtos derivados da Nox2 na patogênese da sepse
• Beneficiário: Silvia Cellone Trevelin
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/07651-1 - Papel dos liver X Receptors-LXRs na modulação da resposta local e sistêmica durante a sepse
• Beneficiário: Fabrício Oliveira Souto
• Modalidade de apoio: Bolsas no Brasil - Doutorado