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Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating Treg/Th17 disorder.

Cheng H, Xi Y, Chi X, Wu Y, Liu G - Cent Eur J Immunol (2016)

Bottom Line: Subsequently, splenocytes were administrated similarly to the test in vivo for detecting cytokine mRNA levels.Compared with the control group, heart weight in EAM group was heavier than in the other groups (p < 0.05), and there was severe inflammatory cell infiltration in heart tissue of the EAM group.Th17 cell-related cytokines mRNA levels in the EAM group/induction group were evidently higher than in other groups (p < 0.05); FOX-p3 mRNA level in the EAM group/induction group was lower than other groups, mRNA levels of IL-10 and FOX-p3 in the fenofibrate group were higher than in the EAM group/induction group (p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiac Function, People's Hospital of Zhengzhou, Zhengzhou City, Henan Province, China.

ABSTRACT

Objective: To investigate the curative effect of fenofibrate on rats with experimental autoimmune myocarditis (EAM) and its immunological mechanism.

Material and methods: Twenty-four rats were equally randomised into three groups: an EAM group, fenofibrate group, and control group, then a subcutaneous injection of purified pig cardiac myosin was given to the EAM group rats and the fenofibrate group, while equivalent normal saline (NS) was given to the control group. After that, the fenofibrate group received fenofibrate by gavage (100 mg/kg/d) and equivalent NS was given to the other groups, lasting for 17 days. Then the rats were sacrificed in order to take heart tissues; HE staining and qRT-PCR method was used to assess the severity of heart failure and mRNA level of cytokines; NK-κB protein content was analyzed by Western-blot. Healthy rat spleen tissue was prepared for splenocyte suspension. Subsequently, splenocytes were administrated similarly to the test in vivo for detecting cytokine mRNA levels.

Results: Compared with the control group, heart weight in EAM group was heavier than in the other groups (p < 0.05), and there was severe inflammatory cell infiltration in heart tissue of the EAM group. Th17 cell-related cytokines mRNA levels in the EAM group/induction group were evidently higher than in other groups (p < 0.05); FOX-p3 mRNA level in the EAM group/induction group was lower than other groups, mRNA levels of IL-10 and FOX-p3 in the fenofibrate group were higher than in the EAM group/induction group (p < 0.05). Fenofibrate could significantly inhibit the up-regulation of NF-κB protein in EAM rats (p < 0.05).

Conclusions: By inhibiting the development of Th17 cells and promoting the differentiation of Tregs, fenofibrate alleviated Treg/Th17 disorder and inhibited inflammation in rats with EAM, thus improving the prognosis.

No MeSH data available.


Related in: MedlinePlus

Body weight, heart weight, the ratio of heart weight/body weight (HW/BW), and mRNA expression level of ANP and BNP in heart tissues of rats (eight rats per group). A) Body weight and heart weight; B) the ratio of heart weight/body weight, HW/BW; C) ANP mRNA expression; D) BNP mRNA expression
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Figure 0001: Body weight, heart weight, the ratio of heart weight/body weight (HW/BW), and mRNA expression level of ANP and BNP in heart tissues of rats (eight rats per group). A) Body weight and heart weight; B) the ratio of heart weight/body weight, HW/BW; C) ANP mRNA expression; D) BNP mRNA expression

Mentions: Compared with the control group, the heart weight of the EAM group was heavier than in the control group and the fenofibrate group (p < 0.05); the ratio of heart weight/body weight (HW/BW) of the EAM group and the fenofibrate group were both higher than in the control group (p < 0.05) (Fig. 1A, B). The mRNA contents of ANP and BNP in the EAM group and the fenofibrate group were higher than those in the control group, and those in the fenofibrate group were lower than in the EAM group (p < 0.05) (Fig. 1C, 1D). Figure 2 showed that there was no inflammatory cell infiltration in the control group, while there was severe inflammatory cell infiltration in the EAM group and slight inflammatory cell infiltration in the fenofibrate group.


Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating Treg/Th17 disorder.

Cheng H, Xi Y, Chi X, Wu Y, Liu G - Cent Eur J Immunol (2016)

Body weight, heart weight, the ratio of heart weight/body weight (HW/BW), and mRNA expression level of ANP and BNP in heart tissues of rats (eight rats per group). A) Body weight and heart weight; B) the ratio of heart weight/body weight, HW/BW; C) ANP mRNA expression; D) BNP mRNA expression
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829822&req=5

Figure 0001: Body weight, heart weight, the ratio of heart weight/body weight (HW/BW), and mRNA expression level of ANP and BNP in heart tissues of rats (eight rats per group). A) Body weight and heart weight; B) the ratio of heart weight/body weight, HW/BW; C) ANP mRNA expression; D) BNP mRNA expression
Mentions: Compared with the control group, the heart weight of the EAM group was heavier than in the control group and the fenofibrate group (p < 0.05); the ratio of heart weight/body weight (HW/BW) of the EAM group and the fenofibrate group were both higher than in the control group (p < 0.05) (Fig. 1A, B). The mRNA contents of ANP and BNP in the EAM group and the fenofibrate group were higher than those in the control group, and those in the fenofibrate group were lower than in the EAM group (p < 0.05) (Fig. 1C, 1D). Figure 2 showed that there was no inflammatory cell infiltration in the control group, while there was severe inflammatory cell infiltration in the EAM group and slight inflammatory cell infiltration in the fenofibrate group.

Bottom Line: Subsequently, splenocytes were administrated similarly to the test in vivo for detecting cytokine mRNA levels.Compared with the control group, heart weight in EAM group was heavier than in the other groups (p < 0.05), and there was severe inflammatory cell infiltration in heart tissue of the EAM group.Th17 cell-related cytokines mRNA levels in the EAM group/induction group were evidently higher than in other groups (p < 0.05); FOX-p3 mRNA level in the EAM group/induction group was lower than other groups, mRNA levels of IL-10 and FOX-p3 in the fenofibrate group were higher than in the EAM group/induction group (p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiac Function, People's Hospital of Zhengzhou, Zhengzhou City, Henan Province, China.

ABSTRACT

Objective: To investigate the curative effect of fenofibrate on rats with experimental autoimmune myocarditis (EAM) and its immunological mechanism.

Material and methods: Twenty-four rats were equally randomised into three groups: an EAM group, fenofibrate group, and control group, then a subcutaneous injection of purified pig cardiac myosin was given to the EAM group rats and the fenofibrate group, while equivalent normal saline (NS) was given to the control group. After that, the fenofibrate group received fenofibrate by gavage (100 mg/kg/d) and equivalent NS was given to the other groups, lasting for 17 days. Then the rats were sacrificed in order to take heart tissues; HE staining and qRT-PCR method was used to assess the severity of heart failure and mRNA level of cytokines; NK-κB protein content was analyzed by Western-blot. Healthy rat spleen tissue was prepared for splenocyte suspension. Subsequently, splenocytes were administrated similarly to the test in vivo for detecting cytokine mRNA levels.

Results: Compared with the control group, heart weight in EAM group was heavier than in the other groups (p < 0.05), and there was severe inflammatory cell infiltration in heart tissue of the EAM group. Th17 cell-related cytokines mRNA levels in the EAM group/induction group were evidently higher than in other groups (p < 0.05); FOX-p3 mRNA level in the EAM group/induction group was lower than other groups, mRNA levels of IL-10 and FOX-p3 in the fenofibrate group were higher than in the EAM group/induction group (p < 0.05). Fenofibrate could significantly inhibit the up-regulation of NF-κB protein in EAM rats (p < 0.05).

Conclusions: By inhibiting the development of Th17 cells and promoting the differentiation of Tregs, fenofibrate alleviated Treg/Th17 disorder and inhibited inflammation in rats with EAM, thus improving the prognosis.

No MeSH data available.


Related in: MedlinePlus