Siglec-G Deficiency Ameliorates Hyper-Inflammation and Immune Collapse in Sepsis via Regulating Src Activation.

Autor:	Li W; Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, China., Li Y; Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China., Qin K; Central Laboratory, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, China., Du B; The Second Affiliated Hospital of Nantong University, Nantong, China., Li T; National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, Shanghai, China., Yuan H; Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, China., Han C; National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, Shanghai, China., Luo Y; Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2019 Nov 07; Vol. 10, pp. 2575. Date of Electronic Publication: 2019 Nov 07 (Print Publication: 2019).
DOI:	10.3389/fimmu.2019.02575
Abstrakt:	Hyper-inflammation during acute phase and sequential hypo-inflammation during immunosuppressive phase in macrophages/monocytes lead to multiorgan failure syndrome and immune collapse of sepsis, in which toll-like receptor (TLR)-triggered inflammatory responses play a major role. Here, we reported that Siglecg deficiency attenuated TLR4-triggered pro-inflammatory cytokine production and increased anti-inflammatory cytokine [interleukin-10 [IL-10]] production in vivo and in vitro at both acute and immunosuppressive phases. Siglecg deficiency also protected mice from lipopolysaccharide (LPS)-induced sepsis with less inflammation in the lung and less tissue destruction in the spleen. Siglec-G inhibited proto-oncogene tyrosine-protein kinase Src (Src) activation via recruiting and activating tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP1) through immunoreceptor tyrosine-based inhibitory motif (ITIM) domain. Src could inhibit TLR4-induced inflammatory cytokines and promote anti-inflammatory cytokine IL-10. Mechanical investigation showed that Src could interact with and phosphorylate STAT3. Src could also promote HIF1α degradation through activating GSK3β. Our study reveals that Siglec-G orchestrates TLR-induced inflammation, which outlines that blocking Siglec-G or activating Src may be a promising strategy for both acute and chronic inflammatory diseases. (Copyright © 2019 Li, Li, Qin, Du, Li, Yuan, Han and Luo.)
Databáze:	MEDLINE
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