Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production (Nat Med, 2009, 15:42-49)

報告日期: 2009/03/10
報告時間: 17:10/18:00
報告學生: 呂秀菱(英文報告)
講評老師: 何漣漪
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980310-3.pdf

Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production

 

Németh K. et al., Nature Medicine 15, 42-49, 2009

 

Speaker: Shiou-Ling Lu

Commentator: Dr. Lien-I Hor 

Time: 2009/3/10, 17:00 ~ 18:00

Place: Room 602

 

Abstract:

    Sepsis causes human high mortality worldwide. In clinical, antibiotics is one of the major treatment; however, most of people die from acute myocardial infarction, since antibiotics has failed to control systemic inflammation and coagulation. Bone marrow stromal cells (BMSCs - as mesenchymal stem cells) have been shown capable of modulating immune responses and have been given to humans as a treatment for transplantation rejection.1 In this study, the authors used cecal ligation and puncture (CLP) as a sepsis model to evaluate whether BMSCs attenuate sepsis in mice. They found that BMSCs treatment improved survival rate and organ function after CLP due to increased interleukin 10 (IL-10) secretion from macrophages. Lipopolysaccharide (LPS)-stimulated BMSCs induced MyD88, NF-kB, and COX2 activation and further released prostaglandin E2 to act on macrophages through the prostaglandin EP2 and EP4 receptors. In addition, the expression of TNF-a, iNOS, and NO by macrophages was also required for COX2 activation and prostaglandin E2 release from BMSCs. The BMSCs that reprogram macrophages, but not other immune cell subtypes, to produce IL-10 is the major effect in sepsis. IL-10, an anti-inflammatory cytokine, could inhibit the migration of neutrophils into the tissue and maintain higher neutrophil counts in the circulation hence to reduce blood bacterial load. BMSCs treatment also reduced CLP-induced vascular permeability. All of the results suggest that BMSCs have many beneficial effects in sepsis. For human treatment, BMSCs are easily cultured and may be used without human leukocyte antigen matching. Most importantly, BMSCs hold a great promise in treating sepsis in high-risk patients.

 

Reference:

1. Le Blanc, K. et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371, 1579–1586, 2008.