TY - JOUR
T1 - Lipoxin A4 protects against lipopolysaccharide-induced sepsis by promoting innate response activator B cells generation
AU - Cheng, Qiong
AU - Wang, Zheng
AU - Ma, Ruihua
AU - Chen, Yongtao
AU - Yan, Yan
AU - Miao, Shuo
AU - Jiao, Jingyu
AU - Cheng, Xue
AU - Kong, Lingfei
AU - Ye, Duyun
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China ( 81502415 ). We thank Prof. Bo Huang (Chinese Academy of Medical Sciences) for comments and suggestions during manuscript preparation and Dr. Ke Tang for technical assistance with Flow cytometry assay.
Publisher Copyright:
© 2016
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Sepsis is a serious disease that leads to severe inflammation, dysregulation of immune system, multi-organ failure and death. Innate response activator (IRA) B cells, which produce granulocyte-macrophage colony-stimulating factor (GM-CSF), protect against microbial sepsis. Lipid mediator lipoxin A4 (LXA4) exerts anti-inflammatory and immunoregulatory effects, and it has been reported that LXA4 receptor ALX/FPR2 is expressed on B cells. Here, we investigated the potential role of LXA4 on IRA B cells in lipopolysaccharide (LPS)-induced sepsis. We found that LXA4 significantly promoted the expansion of splenic IRA B cells and increased GM-CSF expression in splenic B cells with LPS stimulation. After splenectomy, LXA4 treatment did not change the serum or peritoneal IL-1β, IL-6 and TNF-α levels in LPS-induced sepsis. LXA4 accelerated the migration of peritoneal B cells to spleen for their differentiation into IRA B cells, whereas this effect was independent of peritoneal macrophage. Furthermore, LXA4 enhanced the phosphorylation level of signal transducer and activator of transcription 5 (STAT5) in splenic B cells. These results suggest that LXA4 protects against LPS-induced sepsis by promoting the generation and migration of splenic IRA B cells, and the underlying molecular mechanism may be related to STAT5 activation. It might provide new insights and therapeutic approaches for treating sepsis.
AB - Sepsis is a serious disease that leads to severe inflammation, dysregulation of immune system, multi-organ failure and death. Innate response activator (IRA) B cells, which produce granulocyte-macrophage colony-stimulating factor (GM-CSF), protect against microbial sepsis. Lipid mediator lipoxin A4 (LXA4) exerts anti-inflammatory and immunoregulatory effects, and it has been reported that LXA4 receptor ALX/FPR2 is expressed on B cells. Here, we investigated the potential role of LXA4 on IRA B cells in lipopolysaccharide (LPS)-induced sepsis. We found that LXA4 significantly promoted the expansion of splenic IRA B cells and increased GM-CSF expression in splenic B cells with LPS stimulation. After splenectomy, LXA4 treatment did not change the serum or peritoneal IL-1β, IL-6 and TNF-α levels in LPS-induced sepsis. LXA4 accelerated the migration of peritoneal B cells to spleen for their differentiation into IRA B cells, whereas this effect was independent of peritoneal macrophage. Furthermore, LXA4 enhanced the phosphorylation level of signal transducer and activator of transcription 5 (STAT5) in splenic B cells. These results suggest that LXA4 protects against LPS-induced sepsis by promoting the generation and migration of splenic IRA B cells, and the underlying molecular mechanism may be related to STAT5 activation. It might provide new insights and therapeutic approaches for treating sepsis.
KW - B cells
KW - Granulocyte-macrophage colony-stimulating factor
KW - Lipoxin A4
KW - Sepsis
KW - Signal transducer and activator of transcription 5
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U2 - 10.1016/j.intimp.2016.07.026
DO - 10.1016/j.intimp.2016.07.026
M3 - Article
C2 - 27494686
AN - SCOPUS:84979912980
SN - 1567-5769
VL - 39
SP - 229
EP - 235
JO - International Immunopharmacology
JF - International Immunopharmacology
ER -