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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Liver X Receptor Activation Impairs Neutrophil Functions and Aggravates Sepsis

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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]
Total Authors: 10
[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
Total Affiliations: 6
Document type: Journal article
Source: Journal of Infectious Diseases; v. 221, n. 9, p. 1542-1553, MAY 1 2020.
Web of Science Citations: 0

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)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/03293-3 - Role of Nox2 derived products in the pathogenesis of sepsis
Grantee:Silvia Cellone Trevelin
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 09/07651-1 - Role of liver X Receptor-LXRs in the modulation of local and systemic response during sepsis
Grantee:Fabrício Oliveira Souto
Support Opportunities: Scholarships in Brazil - Doctorate