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ABSTRACT: To evaluate the expression of interleukin (IL)-21 in a cigarette smoke-induced mice model of emphysema and explore its effects on the differentiation of CD4(+)T cell.
Twenty male Balb/c mice were randomly divided into two groups: control group and smoke-exposed group. Morphological changes were evaluated by mean linear intercepts and alveolar destructive index. The proportion of CD4(+)IL-21R(+)T cells in lungs of mice was determined by flow cytometry. And the levels of IL-21 in lungs of mice were analyzed by enzyme-linked immunosorbent assay (ELISA). Fresh lung mononuclear cells were isolated from the smoke-exposed group and divided further into two sub-groups: blank sub-group and co-culture sub-group. Two sub-groups were cultured in medium with or without IL-21 for 24 h and 48 h. The proportions of Th1 and Th17 cells in cell culture medium were determined by flow cytometry.
Mean linear intercepts and alveolar destructive index in the smoke-exposed group ((48.6 ± 4.8) µm and 44.9 ± 2.8) were significantly higher than the control group ((32.4 ± 4.0) µm and 28.1 ± 2.1, both P < 0.05). In lungs, the percentage of CD4(+)IL-21R(+)T cells in the smoke-exposed group (4.1% ± 1.5%) significantly increased than that in the control group (1.4% ± 0.4%) (P < 0.05). The levels of IL-21 in lung of the smoke-exposed group ((851 ± 28) ng/L) were higher than those in the control group ((415 ± 39) ng/L, P < 0.05). In lungs, the levels of IL-21 had positive correlations with mean linear intercepts and alveolar destructive index (r = 0.892 and 0.955, both P < 0.05). The percentages of Th1 and Th17 cells in cell culture medium of the co-culture sub-group for 24 h and 48 h significantly increased versus those in the blank group (all P < 0.05).
IL-21 may participate in the occurrence and development of emphysema through the induced differentiation of CD4(+)T cells and the promotion of Th1 and Th17-cell responses in lungs.
Zhonghua yi xue za zhi 04/2012; 92(16):1129-32.
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ABSTRACT: Emphysema is a T-cell mediated autoimmune disease caused predominantly by cigarette smoking. Th17 cells and related cytokines may contribute to this disorder. However, the possible implication of Th17 cells in regulating inflammatory response in emphysema remains to be elucidated. In the current study, we tested the protein levels of IL-17 and IL-21 in peripheral blood and lung tissues from cigarette-smoke- (CS-) exposed mice and air-exposed mice, analyzed the frequencies of CD4(+)IL-17(+)(Th17) cells, IL-21(+)Th17 cells, and CD8(+)IL-21R(+) T cells in peripheral blood and lung tissues of mice, and their relationship with emphysematous lesions, and explored the impact of IL-21 on cytotoxic CD8(+) T cells function in vitro. It was found that the frequencies of Th17, IL-21(+)Th17, and CD8(+)IL-21R(+) T cells and the levels of IL-17 and IL-21 of CS-exposed mice were much higher than those of the air-exposed mice and correlated with emphysematous lesions. Additionally, the number of IL-21(+)Th17 cells positively correlated with the number of CD8(+)IL-21R(+) T cells. The in vitro experiments showed that IL-21 significantly augmented the secretion of perforin and granzyme B in CD8(+) T cells from CS-exposed mice. These data indirectly provide evidence that Th17 cells could be involved in the control of the local and system inflammatory response in emphysema by regulating CD8(+) cytotoxic T-cell function.
Mediators of Inflammation 01/2012; 2012:898053. · 3.26 Impact Factor
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ABSTRACT: To evaluate the expression of Tc17 in a cigarette smoke-induced mice model of emphysema. To explore the probable mechanisms about how Tc17 cells to elevate in lungs of mice.
Forty male Balb/c mice were randomly divided into four groups, including control group (12 weeks, C12), control group (24 weeks, C24), smoke-exposure group (12 weeks, S12) and smoke-exposure group (24 weeks, S24), 10 mice each group, Emphysema of mice was observed by HE pigmentation. Morphological changes were evaluated by mean linear intercepts (Lm) and destructive index (DI). The proportion of CD(8)(+)IL-17(+)Tc17, CD(8)(+)IL-17(+) CC chemokine receptor type 6 (CCR6)(+) and 6CCR6(+)Tc17 cells in lungs of mice was determined by flow cytometry. The mRNA expressions of retinoid-related orphan nuclear receptor (RORγt) and IL-17 were evaluated by real-time PCR. The levels of IL-1β, IL-6, IL-23, transforming growth factor β (TGFβ) and CC chemokine ligand 20(CCL20) were tested by ELISA. Correlations among these indexes were analyzed.
Lm and DI were significantly higher in S12 and S24 than in C12 and C24, S24 in particular (t value 4.378 - 15.188, all P < 0.05). The percentages of Tc17 in S12 and S24 [(9.28 ± 1.12)%, (13.13 ± 3.56)%] was significantly increased as compared with that in C12 and C24 [(2.40 ± 0.60)%, (2.64 ± 0.96)%], S24 in particular. The mRNA levels of RORγt and IL-17 in S12 and S24 were higher than in C12 and C24, S12 and S24 in particular. There was significant difference (all P < 0.05). The frequency of Tc17 cells had a positive correlation with Lm and DI (r value were 0.734 and 0.884 respectively, P < 0.01). The percentages of CD(8)(+)IL-17(+)CCR6(+)T cells and CCR6(+)Tc17 were significantly elevated in S12 and S24 compared to C12 and C24, S24 in particular (all P < 0.05). There was positive correlation between Tc17 cell ratio and CCL20 levels (r = 0.899, P < 0.01). The levels of IL-1β, IL-6, IL-23 and TGFβ in S12 and S24 were significantly increased as compared with that in C12 and C24. There was significant difference (all P < 0.05). Meanwhile, the frequency of Tc17 cells had a positive correlation with IL-1β, IL-6, IL-23, and TGFβ.
An up-regulation of proportions Tc17 in lungs of cigarette smoke-induced emphysema mice were detected. The CCR6/CCL20 axis and the increased IL-1β, IL-6, IL-23 and TGFβ probably contributed to this up-regulation.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 09/2011; 50(9):776-80.
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ABSTRACT: To evaluate the expression of Th17 cell in a cigarette smoke-induced mice model of emphysema and explore the probable mechanisms of its elevation.
Forty male Balb/c mice were randomly divided into 4 groups: control group for 12 weeks (C12), control group for 24 weeks (C24), smoke-exposure group for 12 weeks (S12) and smoke-exposure group for 24 weeks (S24)(n = 10 each). Morphological changes were evaluated by mean linear intercepts (Lm) and destructive index (DI). The percentages of Th17, Th1, Th17/Th1, CD4(+)IL-17(+)CCR6(+)T and CCR6(+)Th17 cells were determined by tetra-color flow cytometry while the levels of interleukin (IL)-1β, IL-6, IL-23, transforming growth factor (TGF)-β, interferon (IFN)-γ and CC chemokine ligand (CCL)-20 assayed by enzyme-linked immunosorbent assay (ELISA).
The values of Lm [(39 ± 4) µm, (47 ± 7) µm] and DI [(39.1 ± 1.6), (45.2 ± 3.1)] were significantly higher in S12 and S24 than those in C12 [(33 ± 3) µm, (28.2 ± 1.6)] and C24 [(32 ± 4) µm, (28.9 ± 2.1)], particularly in C24 (all P < 0.05). The percentages of Th17 cell [(3.27 ± 1.12), (7.19 ± 2.24)], Th17/Th1 cell [(0.61 ± 0.30), (1.82 ± 0.52)] and Th1 cell [(10.02 ± 3.68), (26.21 ± 6.04)] in the lungs of S12 and S24 significantly increased than those in C12 [(1.80 ± 0.75), (0.27 ± 0.12), (3.75 ± 1.72)] and C24 [(1.99 ± 0.59), (0.28 ± 0.11), (4.16 ± 1.32)], particularly in C24 (all P < 0.01). The percentages of Th17, Th17/Th1 and Th1 cells in the lungs of S12 and S24 had a positive correlation with Lm and DI (all P < 0.01). The percentages of CD4(+)IL-17(+)CCR-6(+)T cell [(0.69 ± 0.34), (1.11 ± 0.48)] and CCR6(+)Th17 cell [(12.23 ± 2.13), (18.65 ± 1.17)] were significantly elevated in S12 and S24 compared to those in C12 [(0.22 ± 0.18), (6.55 ± 2.13)] and C24 [(0.25 ± 0.17), (7.29 ± 1.57)], particularly in C24 (all P < 0.05). Furthermore, a positive correlation between CCR6(+)Th17 cell and emphysematous lesions was also found (all P < 0.05). The levels of IL-1β, IL-6, IL-23, TGF-β, IFN-γ and CCL20 significantly increased in S12 and S24 as compared with those of C12 and C24 (all P < 0.05). Meanwhile, the percentage of Th17 cell had a positive correlation with IL-1β, IL-6, IL-23, TGF-β, IFN-γ and CCL20.
There is an up-regulated expression of Th17 in lungs of cigarette smoke-induced emphysema mice. The CCR6/CCL20 axis and the elevated levels of IL-1β, IL-6, IL-23, TGF-β and IFN-γ may be related with the above effect.
Zhonghua yi xue za zhi 07/2011; 91(28):1996-2000.
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ABSTRACT: 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.
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 04/2011; 34(4):259-64.
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Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 12/2010; 33(12):921-3.
