Duan Min-chao, Zhong Xiao-ning, He Zhi-yi, Tang Hai-juan, Huang Ying
Department of Respiratory Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2011 Apr;34(4):259-64.
To evaluate the expression and the role of Th17 in cigarette smoke-induced lung inflammation and emphysema in mice.
Forty male BALB/c mice were randomly divided into 4 groups, including a control group C12, a control group C24, a smoke-exposure 12 week group (S12) and a smoke-exposure 24 week group S24 (n = 10 each). Morphological changes were evaluated by mean linear intercepts and destructive index (DI). The proportion of CD(4)(+)IL-17(+)Th17, CD(4)(+)IFN-γ(+)Th1, CD(4)(+)IL-17(+)IFN-γ(+)T(Th17/Th1), CD(8)(+)IFN-γ(+)Tc1, CD(8)(+)IL-21R(+) and CD(4)(+)IL-17(+)IL-21(+) T cells in lungs of mice was determined by flow cytometry. The mRNA expressions of RORγt and IL-17 were evaluated by real-time PCR.
Mean linear intercepts and DI were significantly higher in S12 and S24 groups [(39 ± 4) µm, (47 ± 7) µm], (39.1 ± 1.6, 45.2 ± 3.1) as compared to C12 [(32 ± 4) µm, 28.2 ± 1.6] and C24 groups [(33 ± 3) µm, 28.9 ± 2.1], all P < 0.05. The percentage of Th17 of S12 and S24 groups [(3.3 ± 1.1)%, (7.2 ± 2.2)%] was significantly increased as compared with that of C12 and C24 groups [(1.8 ± 0.8)%, (2.0 ± 0.6)%], all P < 0.05. The mRNA levels of RORγt [(25 ± 4), (35 ± 3)] and IL-17 [(26 ± 3), (36 ± 3)] in S12 and S24 groups were higher than in C12 [(10 ± 5), (13 ± 5)] and C24 groups [(11 ± 7), (8 ± 6)], all P < 0.05. The percentage of Th1, Th17/Th1 and Tc1 cells of S12 and S24 groups [(10.0 ± 3.7)%, (26.2 ± 6.0)%], [(0.61 ± 0.30)%, (1.82 ± 0.52)%], [(17.0 ± 4.5)%, (26.8 ± 8.5)%] was significantly increased as compared with that of C12 [(3.8 ± 1.7)%, (0.27 ± 0.17)%, (4.8 ± 1.9)%] and C24 groups [(4.2 ± 1.3)%, (0.28 ± 0.11)%, (5.2 ± 1.0)%], all P < 0.05. Moreover, the frequency of Th17 cells had a positive correlation with Th1, Tc1 cells and emphysematous lesions (r = 0.519 - 0.797, all P < 0.01). In addition, a positive correlation between Th17/Th1 cells and emphysematous lesions was also found (r = 0.742, 0.802, all P < 0.01). The percentage of CD(4)(+)IL-17(+)IL-21(+) T cells was significantly increased in S12 and S24 groups [(0.19 ± 0.04)%, (0.55 ± 0.24)%] compared to controls [(0.07 ± 0.03)%, (0.08 ± 0.03)%], all P < 0.05. Meanwhile, as compared with that of the controls [(1.22 ± 0.31), (1.34 ± 0.18)], the percentage of CD(8)(+)IL-21R(+) T cells was also increased in S12 and S24 groups [(2.94 ± 1.26), (4.12 ± 2.26)], but there were no differences among smoke-exposure groups (P > 0.05). The frequency of CD(4)(+)IL-17(+)IL-21(+) T cells had a positive correlation with Th1, Tc1 cells and emphysematous lesions (r = 0.694 - 0.754, all P < 0.05). And the frequency of CD(8)(+)IL-21R(+) T cells also had a positive correlation with emphysematous lesions (r = 0.516, 0.725, all P < 0.05).
Cigarette smoke increased the expression and the activity of Th17 in mice. Th17 may play a potential (active) role in the development of lung inflammation through IL-21/IL-21R pathway.
评估Th17在香烟烟雾诱导的小鼠肺部炎症和肺气肿中的表达及作用。
将40只雄性BALB/c小鼠随机分为4组，包括对照组C12、对照组C24、烟雾暴露12周组（S12）和烟雾暴露24周组S24（每组n = 10）。通过平均线性截距和破坏指数（DI）评估形态学变化。采用流式细胞术测定小鼠肺组织中CD(4)(+)IL-17(+)Th17、CD(4)(+)IFN-γ(+)Th1、CD(4)(+)IL-17(+)IFN-γ(+)T(Th17/Th1)、CD(8)(+)IFN-γ(+)Tc1、CD(8)(+)IL-21R(+)及CD(4)(+)IL-17(+)IL-21(+) T细胞的比例。采用实时PCR评估RORγt和IL-17的mRNA表达。
与C12组[(32 ± 4) µm, 28.2 ± 1.6]和C24组[(33 ± 3) µm, 28.9 ± 2.1]相比，S12组和S24组的平均线性截距和DI显著更高[(39 ± 4) µm, (47 ± 7) µm]，(39.1 ± 1.6, 45.2 ± 3.1)，所有P < 0.05。与C12组[(1.8 ± 0.8)%, (2.0 ± 0.6)%]和C24组相比，S12组和S24组的Th17百分比[(3.3 ± 1.1)%, (7.2 ± 2.2)%]显著增加，所有P < 0.05。S12组和S24组中RORγt[(25 ± 4), (35 ± 3)]和IL-17[(26 ± 3), (36 ± 3)]的mRNA水平高于C12组[(10 ± 5), (13 ± 5)]和C24组[(11 ± 7), (8 ± 6)]，所有P < 0.05。与C12组[(3.8 ± 1.7)%, (0.27 ± 0.17)%, (4.8 ± 1.9)%]和C24组[(4.2 ± 1.3)%, (0.28 ± 0.11)%, (5.2 ± 1.0)%]相比，S12组和S24组的Th1、Th17/Th1及Tc1细胞百分比[(10.0 ± 3.7)%, (26.2 ± 6.0)%]，[(0.61 ± 0.30)%, (1.82 ± 0.52)%]，[(17.0 ± 4.5)%, (26.8 ± 8.5)%]显著增加，所有P < 0.05。此外，Th17细胞频率与Th1、Tc1细胞及肺气肿病变呈正相关（r = 0.519 - 0.797，所有P < 0.01）。另外，还发现Th17/Th1细胞与肺气肿病变之间存在正相关（r = 0.742, 0.802，所有P < 0.01）。与对照组[(0.07 ± 0.03)%, (0.08 ± 0.03)%]相比，S12组和S24组中CD(4)(+)IL-17(+)IL-21(+) T细胞百分比显著增加[(0.19 ± 0.04)%, (0.55 ± 0.24)%]，所有P < 0.05。同时，与对照组[(1.22 ± 0.31), (1.34 ± 0.18)]相比，S12组和S24组中CD(8)(+)IL-21R(+) T细胞百分比也增加[(2.94 ± 1.26), (4.12 ± 2.26)]，但烟雾暴露组之间无差异（P > 0.05）。CD(4)(+)IL-17(+)IL-21(+) T细胞频率与Th1、Tc1细胞及肺气肿病变呈正相关（r = 0.694 - 0.754，所有P < 0.05）。并且CD(8)(+)IL-21R(+) T细胞频率也与肺气肿病变呈正相关（r = 0.516, 0.725，所有P < 0.05）。
香烟烟雾增加了小鼠Th17的表达和活性。Th17可能通过IL-21/IL-21R途径在肺部炎症发展中发挥潜在（积极）作用。
