International journal of surgery (London, England) · 2025
TREM1 deficiency attenuates LPS-induced sepsis-associated acute kidney injury by modulating macrophage polarization.
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Xu Ye, Fan Yuxi, Peng Jiawei, Zhang Xiangqi, Luo Qiulin, Shui Kankan, Li Tengfang, Qin Jiajie, Zhang Hedong, Nie Rongzheng, Zhong Yanjun, Jiang Xin, Jin Xuefei, Xu Min, Peng Longkai, Dai Helong
Аннотация
BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) drives high mortality in sepsis. The triggering receptor expressed on myeloid cells-1 (TREM1) plays critical roles in both infectious and non-infectious pathologies. However, the role of TREM1 in AKI still needs to be further clarified.
METHODS: Using both in vivo and in vitro experiments, we examined the role and underlying mechanism of TREM1 in AKI.
RESULTS: In this study, the level of soluble TREM (sTREM1) in the urine of patients with SA-AKI was significantly higher than that of the healthy control group, although there was no significant difference in sTREM1 levels in the serum. In the SA-AKI mouse model, TREM1 deficiency markedly reduced serum creatinine levels in SA-AKI mice. Notably, TREM1 deficiency significantly promoted the expression levels of Il10 and Cd206 in the kidneys of SA-AKI mice. Cytometric Bead Array analysis revealed that serum levels of the pro-inflammatory cytokines IL17A and IFN-γ were significantly diminished, whereas the anti-inflammatory factor IL10 was notably elevated. The enzyme-linked immunosorbent assay (ELISA) results showed that the serum levels of CCL2 and CXCL1 in TREM1-deficient mice were significantly reduced. Mechanistically, experimental evidence indicated that TREM1 deficiency promoted M2 macrophage polarization by activating IRF4 via PI3K/AKT and STAT6 pathways.
CONCLUSIONS: These findings confirmed that TREM1 is the primary regulatory factor of macrophage plasticity in SA-AKI, proposing a therapeutic strategy for the clinical intervention of SA-AKI-related kidney diseases.
METHODS: Using both in vivo and in vitro experiments, we examined the role and underlying mechanism of TREM1 in AKI.
RESULTS: In this study, the level of soluble TREM (sTREM1) in the urine of patients with SA-AKI was significantly higher than that of the healthy control group, although there was no significant difference in sTREM1 levels in the serum. In the SA-AKI mouse model, TREM1 deficiency markedly reduced serum creatinine levels in SA-AKI mice. Notably, TREM1 deficiency significantly promoted the expression levels of Il10 and Cd206 in the kidneys of SA-AKI mice. Cytometric Bead Array analysis revealed that serum levels of the pro-inflammatory cytokines IL17A and IFN-γ were significantly diminished, whereas the anti-inflammatory factor IL10 was notably elevated. The enzyme-linked immunosorbent assay (ELISA) results showed that the serum levels of CCL2 and CXCL1 in TREM1-deficient mice were significantly reduced. Mechanistically, experimental evidence indicated that TREM1 deficiency promoted M2 macrophage polarization by activating IRF4 via PI3K/AKT and STAT6 pathways.
CONCLUSIONS: These findings confirmed that TREM1 is the primary regulatory factor of macrophage plasticity in SA-AKI, proposing a therapeutic strategy for the clinical intervention of SA-AKI-related kidney diseases.