Correlation between overexpression of TLR4/MyD88 signaling and intestinal graft-versus-host disease after allogeneic bone marrow transplantation in mice
10.3760/cma.j.issn.0254-1785.2014.07.012
- VernacularTitle:小鼠异基因骨髓移植后TLR4/MyD88信号过表达与肠道急性GVHD的相关性
- Author:
Shuai XING
;
Xue ZHANG
;
Xia HUANG
;
Ping ZHOU
- Publication Type:Journal Article
- Keywords:
Mice;
Bone marrow transplantation;
Graft-versus-host disease
- From:
Chinese Journal of Organ Transplantation
2014;35(7):431-435
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the expression of TLR4/MyD88/NF-κB signaling and its correlation with the progression of acute intestinal graft-versus-host disease (iGVHD) after allogeneic bone marrow transplantation in mice.Method Recipient BALB/c female mice were lethally irradiated and were reconstituted within 4-6 h with a transplant of bone marrow cells (1 × 107) and different amounts of splenocytes (1 × 107,n =12 or 2 × 107,n =12) from MHC-mismatched C57BL/6 donors to induce iGVHD,and 6 healthy BALB/c mice served as controls.A globe survey observation of GVHD by survival,clinical manifestation,and histological detection was performed.RT-PCR,immunohistochemistry,and Western blotting technology were used to detect the mRNA and protein levels of TLR4,MyD88 and NF-κB p65 in the small intestine tissue.Result The exacerbation of iGVHD was associated with the increasing dose of allogeneic spleen lymphocytes.The mRNA expression of TLR4,MyD88 and NF-κBp65 was increased as the iGVHD progressed.All of them in severe iGVHD model were significantly increased as compared with the healthy controls (P＜0.05).The expression of corresponding proteins had the same tendency as mRNA.All of the three genes expression was not only positively correlated with each other,but also with the clinical GVHD score:TLR4 (R =0.814,P＜0.001),MyD88 (R=0.828,P＜0.001),and NF-κB p65 (R=0.568,P =0.034).Conclusion Excessive activation of TLR4/MyD88/NF-κB signaling pathway does exist in iGVHD,and the enhanced levels of gene transcription and translation are positively correlated with the deterioration of iGVHD.
