Recombinant Trichinella spiralis 53-kDa protein activates M2 macrophages and attenuates the LPS-induced damage of endotoxemia.
Sepsis is a serious clinical condition of excessive systemic immune response to microbial infection. The pro-inflammatory stage of sepsis is generally launched by innate cells such as macrophages. They release inflammatory cytokines, activate other immune cells and cause severe tissue/organ damage. In this study, we have revealed that recombinant Trichinella spiralis (TS) excretory-secretory protein (rTsP53) exhibited anti-inflammatory properties and rescued mice from LPS-induced endotoxemia, which is a common model for sepsis study, potentially through the induction of M2 macrophages. rTsP53 treatment significantly decreased inflammatory cytokines (IL-6, IFN-γ and TNF-α) and increased IL-4, IL-10, IL-13 and TGF-β secretion, both in circulation and in tissues. rTsP53 also induced the activation and infiltration of F4/80(+)CD163(+) macrophages to inflammatory tissues, increased M2 macrophage-related Arg1 and Fizz1 expression, and decreased M1 macrophage-related iNOS expression. PCR array showed that rTsP53 activated several genes that involve the survival of macrophages and also anti-inflammatory genes such as SOCS3. Together, our results show that rTsP53 activates M2 macrophages, which has strong anti-inflammatory potential to prevent LPS-induced lethal sepsis.
General Internal Medicine Department of The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Zhi-Bin
ZB
Chen
General Internal Medicine Department of The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Hao
H
Tang
General Internal Medicine Department of The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Yan-Bing
YB
Liang
General Internal Medicine Department of The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Wen
W
Yang
General Internal Medicine Department of The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Jing-Guo
JG
Wu
Parasitology Laboratory of Northern Campus, Sun Yat-sen University, Guangzhou, China.
Xu-Chu
XC
Hu
General Internal Medicine Department of The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Zhen-Yu
ZY
Li
General Internal Medicine Department of The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Li-Jin
LJ
Zeng
General Internal Medicine Department of The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China zhongfumafv@yeah.net.
Zhong-Fu
ZF
Ma
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000378:metabolism*; D000947:Antigens, Helminth / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology*; D015801:Helminth Proteins / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D000947:Antigens, Helminth; D016207:Cytokines; D015801:Helminth Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; C097419:excretory-secretory antigen, Trichinella
M2 macrophage; SOCS3; Sepsis; Trichinella spiralis; inflammation