"Chromofungin, a chromogranin A-derived peptide, protects against sepsis-induced acute lung injury by inhibiting LBP/TLR4-dependent inflammatory signaling"

作者全名："Zhou, Wushuang; Kang, Shengnan; Wang, Fenglin; Qin, Yupin; Liu, Jinglun; Xiao, Xiaoqiu; Chen, Xiaoying; Zhang, Dan"

作者地址："[Zhou, Wushuang; Kang, Shengnan; Wang, Fenglin; Qin, Yupin; Zhang, Dan] Chongqing Med Univ, Affiliated Hosp 1, Dept Emergency, Chongqing 400016, Peoples R China; [Liu, Jinglun; Chen, Xiaoying] Chongqing Med Univ, Affiliated Hosp 1, Dept Surg Care Unit, Chongqing 400016, Peoples R China; [Xiao, Xiaoqiu] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Translat Med Major Metab Dis, Chongqing 400016, Peoples R China"

通信作者："Zhang, D (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Emergency, Chongqing 400016, Peoples R China.; Chen, XY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Surg Care Unit, Chongqing 400016, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001079746000001

JCR分区：Q1

影响因子：4.2

年份：2023

卷号：958

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Sepsis-induced acute lung injury; CHR; Macrophage; Polarization; Lipopolysaccharide-binding protein; Toll-like receptor 4

摘要："Chromofungin (CHR) is a biologically active peptide derived from chromogranin A that exhibits antiinflammatory effects. However, it remains unclear whether and how CHR protects against sepsis-induced acute lung injury (ALI). A murine model of sepsis-induced ALI was established through cecal ligation and puncture, with intraperitoneal injection of CHR. Lung inflammation and macrophage polarization were examined by measuring the levels of cytokines and markers of M1 (CD86, inducible nitric oxide synthase [iNOS]) or M2 macrophages (arginase-1 [Arg1], resistin-like molecule alpha 1 [Fizz1] and CD206). In vitro, mouse MH-S cells pretreated with CHR was employed to explore the interplay between the lipopolysaccharide-binding protein (LBP)/toll-like receptor 4 (TLR4) signaling pathway and M1/M2 polarity. The results revealed CHR's ability to enhance the 7-day survival rate and protect lung pathological injury in sepsis-induced ALI. CHR increased the expression of interleukin-4 and interleukin-10 but decreased the expression of tumour necrosis factor-alpha and interleukin-1 beta. In addition, CHR notably facilitated M2 macrophage polarization, while significantly suppressingM1 polarization of alveolar macrophages. Mechanistic investigations delineated CHR's role in macrophage polarization by downregulating nuclear factor-kappa B expression through modulation of the LBP/TLR4 signaling pathway. Therefore, CHR may represent a novel strategy for the prevention of sepsis-induced ALI."

基金机构："Science and Technology Commission of Chongqing [cstc2020jcyj-msxmX0922]; High-level Medical Reserved Personnel Training Project of 12 Chongqing [2020GDRC018]; National Natural Science Foundation of China 13 [81372102, 81071531]; Science and Technology Commission of Chongqing 14 [cstc2020jcyj-msxmX0761, CSTB2022NSCQ-MSX0912]; Science and Technology Commission of 15 Chongqing Yuzhong District [20210138]"

基金资助正文："This work was supported by he Science and Technology Commission of Chongqing (Grants 11 NO. cstc2020jcyj-msxmX0922) , the High-level Medical Reserved Personnel Training Project of 12 Chongqing (Grants NO. 2020GDRC018) , the National Natural Science Foundation of China 13 (Grants NO. 81372102, 81071531) , the Science and Technology Commission of Chongqing 14 (Grants NO. cstc2020jcyj-msxmX0761, CSTB2022NSCQ-MSX0912) and the Science and Technology Commission of 15 Chongqing Yuzhong District (Grants NO. 20210138) ."