OCH ameliorates bone marrow failure in mice via downregulation of T-bet expression.

Xiaohong Qiao,Wei Shi,Yuexia Shao,Fuxing Li,Jinqing Tang,Xiaotian Xie

doi:10.1155/2014/928743

Abstract

The aim of this study is to evaluate the immune mechanism of OCH in the treatment of AA (also named bone marrow failure, BMF) induced in mice. OCH at a dose of 400 μg/kg was injected intraperitoneally (I.P.) prior to the induction of BMF. Our study showed that the incidence of BMF was 100% in BMF group and 13% in OCH treatment group. Significant higher level of IL-4 and lower level of IFN-γ were observed in OCH group than that in BMF group (P < 0.05) as well as untreated group over BMF (P < 0.05). However, there was no significant difference between OCH and untreated group. Compared with untreated, the expression level of T-bet in OCH and BMF was all significantly higher. However, T-bet expression level was lower in OCH than in BMF. In addition, OCH treatment increased NKT cell fractions of bone marrow and the colonies of CFU-GM. In conclusion, treatment of OCH prior to the induction of BMF could prevent the incidence of BMF possibly through downregulating T-bet expression leading to the transition of immune response from Th1 to Th2, suggesting OCH might be a new therapeutic approach in the treatment of BMF or AA.

Highlights

Aplastic anemia (AA), known as bone marrow failure (BMF), is a blood disorder, characterized by impaired hematopoiesis, leading to pancytopenia [1]
AA has been known as an autoimmune disease, characterized by Th1-mediated abnormal immune response
There are a growing numbers of studies demonstrating the association of abnormal numbers and function of NKT cells with many autoimmune diseases, such as diabetes, multiple sclerosis, and rheumatoid arthritis [8, 16]

Summary

Introduction

Aplastic anemia (AA), known as bone marrow failure (BMF), is a blood disorder, characterized by impaired hematopoiesis, leading to pancytopenia [1]. The pathogenesis of AA is very complicated and the impaired hematopoiesis from bone marrow was reported to be related with abnormal numbers and functions of T lymphocytes as well as dysregulation of cytokine secretion, suggesting that AA was an autoimmune disease, characterized by increased Th1 cells and downstream cytokines [2,3,4]. OCH is a sphingosine truncated derivative of alpha-galactosylceramide (α-GC) and can stimulate NKT cells to selectively produce Th2 cytokines, leading to the transition of immune response from Th1 to Th2 [8]. Previous studies demonstrated different cytokines secretion from NKT cell by different stimulus, with IFN-γ predominant by α-GC stimulation and IL-4 by OCH [9]. Given the critical role in the Th2 immune response via NKT activation, OCH has been under extensive studies as a therapeutic in the treatment of many Th1-related autoimmune diseases, such as experimental encephalomyelitis (EAE), type I diabetes, and collagen-induced arthritis (CIA) [10,11,12,13]

Objectives

Results

Conclusion