Identification of macrophage phenotypes and evaluation of their role in the immunopathogenesis in animal model of Behçet’s disease

Author(s)
Anower, A.K.M. Mostafa
Advisor
Seonghyang Sohn
Department
일반대학원 의생명과학과
Publisher
The Graduate School, Ajou University
Publication Year
2013-02
Language
eng
Alternative Abstract
Although several immunological abnormalities have been demonstrated in Behçet’s disease (BD), the exact mechanism of the inflammatory changes occurring during the development of this disease remains unclear. Macrophage phenotypes are markedly heterogeneous and include classically activated (M1) and alternatively activated (M2) macrophages. In a herpes simplex virus (HSV)-induced BD mouse model, it has confirmed the abundant expression of the M1 phenotype (CD16/32) compared to the M2 phenotype (CD23). For M1/M2 phenotypic transformation in vivo normal mice, recombinant interferon-gamma (rIFN-g) significantly increased the M1/M2 ratio (1.74±0.42) when compared with recombinant interleukin-4 (rIL-4) (0.83±0.20) or the phosphate buffered saline (PBS) treated control (0.66±0.34). In BD mice, rIL-4 treatment decreased the M1/M2 ratio (1.2±0.3) compared to PBS treated (2.4±2.9) or rIFN-g treated groups (2.1±2.3). The M1/M2 ratio in rIL-4 treated BD mice was similar to the asymptomatic BD mice (BD normal, BDN) (1.0±0.9). In BDN mice, rIFN-g or rIL-4 treatment did not affect the M1/M2 ratio (1.2±0.4, 1.2±0.7, respectively). This amelioration of BD-like symptoms was correlated with a decrease in the M1/M2 ratio accompanied by down-regulation of IL-17 and IL-6, and up-regulation of IL-4. Furthermore, colchicine and pentoxifylline, which are frequently prescribed BD medications, decreased the M1/M2 ratio and improved BD-like symptoms in mice. This study clearly demonstrates the correlation of the M1 and M2 macrophage phenotypes and the M1/M2 ratio with HSV-induced BD-like symptoms. Therefore, a shift in the population of macrophages is a pathologic factor and modulation of macrophage phenotypes may have important implications for the treatment of BD. Key words: Behçet’s disease, CD16/32, CD23, colchicine, HSV-induced inflammation, M1/M2 macrophages, mouse model
URI
https://dspace.ajou.ac.kr/handle/2018.oak/18169
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Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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