CD163 deficiency facilitates lipopolysaccharide?induced inflammatory responses and endotoxin shock in mice

ABSTRACT: Abstract Objectives Septic (or endotoxin) shock is a severe systemic inflammatory disease caused by bacteraemia or endotoxaemia. Although it is known that increased serum levels of CD163 are observed in septic/endotoxin shock patients, the exact function and significance of CD163 in macrophage activation remain unclear. Therefore, in the current study, we tested whether CD163 contributes to the pathogenesis of endotoxin shock in mice. Methods and results In samples obtained from autopsy, the number of CD163?positive macrophages was increased in the kidney, liver, heart, bone marrow and spleen of patients who had died from septic/endotoxin shock when compared to patients who had died from other causes. The animal study revealed a significantly lower survival rate in CD163?deficient mice after lipopolysaccharide (LPS) injection. Several cytokines and oxidative stress?related molecules were significantly elevated in the sera of LPS?induced endotoxin shock mice models. Higher concentrations of IL?6, TNF??, IL?1?, nitrite (NO2?) and nitrate (NO3?) and a lower concentration of IL?10 were observed in CD163?deficient mice treated with LPS. Similar results were observed in CD163?deficient LPS?stimulated macrophages. Furthermore, in an antitype II collagen antibody?induced arthritis (CAIA), rheumatoid arthritis model, inflammation and bone erosion scores as well as the expression of IL?6 and IL?1? were significantly increased in CD163?deficient mice. Conclusions CD163 was suggested to be involved in the regulation of inflammatory cytokine expression in septic/endotoxin shock and CAIA. In this study, CD163 suppressed excessive activation of macrophages in human and mice samples. The results also showed that CD163 has a protective role in inflammatory conditions and is involved in the regulation of inflammatory cytokine expression in endotoxin shock.

SUBMITTER: Fujiwara Y 

PROVIDER: S-EPMC7518957 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature