Liver X receptor activation impairs neutrophil functions and aggravates sepsis.

Fabricio Oliveira Souto; Fernanda  Castanheiras; Silvia Cellone Trevelin; Braulio HF Lima; Guilherme Cesar Martelossi; Walter Turato; Maria-Auxiliadora Martins; Anibal Basili-Filho; Jose Carlos Alves-Filho; Fernando Queiroz Cunha

Liver X receptor activation impairs neutrophil functions and aggravates sepsis.

Fabricio Oliveira Souto, Fernanda Castanheiras, Silvia Cellone Trevelin, Braulio HF Lima, Guilherme Cesar Martelossi, Walter Turato, Maria-Auxiliadora Martins, Anibal Basili-Filho, Jose Carlos Alves-Filho, Fernando Queiroz Cunha

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in the several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-β, the consequences of their activation, particularly during sepsis, remain unknown. Here, 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 multi-organ failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load and multi-organ dysfunction. Importantly, neutrophils from septic patients showed increased ABCA1 mRNA levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared to cells from healthy individuals. Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.

Original language	English
Journal	Journal of Infectious Diseases
Publication status	Accepted/In press - 30 Nov 2019

Keywords

inflammation, killing, LXRs, neutrophil migration, sepsis

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https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiz635/5648049Licence: Unspecified

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Oliveira Souto, F., Castanheiras, F., Cellone Trevelin, S., HF Lima, B., Martelossi, G. C., Turato, W., Martins, M.-A., Basili-Filho, A., Alves-Filho, J. C., & Queiroz Cunha, F. (Accepted/In press). Liver X receptor activation impairs neutrophil functions and aggravates sepsis. Journal of Infectious Diseases. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiz635/5648049

@article{bfb537fc62e94db3a51efbc0e425f989,

title = "Liver X receptor activation impairs neutrophil functions and aggravates sepsis.",

abstract = "Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in the several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-β, the consequences of their activation, particularly during sepsis, remain unknown. Here, 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 multi-organ failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load and multi-organ dysfunction. Importantly, neutrophils from septic patients showed increased ABCA1 mRNA levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared to cells from healthy individuals. Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.",

keywords = "inflammation, killing, LXRs, neutrophil migration, sepsis",

author = "{Oliveira Souto}, Fabricio and Fernanda Castanheiras and {Cellone Trevelin}, Silvia and {HF Lima}, Braulio and Martelossi, {Guilherme Cesar} and Walter Turato and Maria-Auxiliadora Martins and Anibal Basili-Filho and Alves-Filho, {Jose Carlos} and {Queiroz Cunha}, Fernando",

year = "2019",

month = nov,

day = "30",

language = "English",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

}

TY - JOUR

T1 - Liver X receptor activation impairs neutrophil functions and aggravates sepsis.

AU - Oliveira Souto, Fabricio

AU - Castanheiras, Fernanda

AU - Cellone Trevelin, Silvia

AU - HF Lima, Braulio

AU - Martelossi, Guilherme Cesar

AU - Turato, Walter

AU - Martins, Maria-Auxiliadora

AU - Basili-Filho, Anibal

AU - Alves-Filho, Jose Carlos

AU - Queiroz Cunha, Fernando

PY - 2019/11/30

Y1 - 2019/11/30

N2 - Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in the several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-β, the consequences of their activation, particularly during sepsis, remain unknown. Here, 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 multi-organ failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load and multi-organ dysfunction. Importantly, neutrophils from septic patients showed increased ABCA1 mRNA levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared to cells from healthy individuals. Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.

AB - Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in the several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-β, the consequences of their activation, particularly during sepsis, remain unknown. Here, 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 multi-organ failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load and multi-organ dysfunction. Importantly, neutrophils from septic patients showed increased ABCA1 mRNA levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared to cells from healthy individuals. Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.

KW - inflammation, killing, LXRs, neutrophil migration, sepsis

M3 - Article

SN - 0022-1899

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

ER -

Liver X receptor activation impairs neutrophil functions and aggravates sepsis.

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Keywords

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