title: Lipoxin A4 protects against lipopolysaccharide-induced sepsis by promoting innate response activator B cells generation.
abstract: 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.
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pathology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
authors: Qiong
authors: Q
authors: Cheng
authors: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Zheng
authors: Z
authors: Wang
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Ruihua
authors: R
authors: Ma
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yongtao
authors: Y
authors: Chen
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yan
authors: Y
authors: Yan
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Shuo
authors: S
authors: Miao
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Jingyu
authors: J
authors: Jiao
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Xue
authors: X
authors: Cheng
authors: Department of Pathology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
authors: Lingfei
authors: L
authors: Kong
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yedy@mails.tjmu.edu.cn.
authors: Duyun
authors: D
authors: Ye
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology; D044045:Lipoxins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D044045:Lipoxins; D050799:STAT5 Transcription Factor; C040527:lipoxin A4
keywords: B cells; Granulocyte-macrophage colony-stimulating factor; Lipoxin A4; Sepsis; Signal transducer and activator of transcription 5