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A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice.

Hirakawa H, Zempo H, Ogawa M, Watanabe R, Suzuki J, Akazawa H, Komuro I, Isobe M - PLoS ONE (2015)

Bottom Line: No specific or effective treatment has been established.DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases.Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT
Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22). Pathological analysis revealed that the myocardial fibrosis area ratio in the treated group was significantly lower than in the untreated group. RT-PCR analysis demonstrated that the levels of mRNA expression of IL-2, TNF-α, IL-1β and IL-6 were significantly lower in the treated group than in the untreated group. Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation. Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents present in DPP-4 inhibitors may be useful to treat and/or prevent clinical myocarditis.

No MeSH data available.


Related in: MedlinePlus

Results of lymphocyte proliferation assay.Cultures with spleen-derived lymphocytes obtained from EAM mice were incubated at 37°C with 5% CO2 for 70 hours. Lymphocyte proliferation was evaluated. Treatment of a DPP-4 inhibitor did not affect antigen-induced spleen-derived lymphocyte proliferation. *P < 0.05 vs. Myosin-, Linagliptin-, Bonferroni comparison test. Values are mean ± SEM.
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pone.0119360.g003: Results of lymphocyte proliferation assay.Cultures with spleen-derived lymphocytes obtained from EAM mice were incubated at 37°C with 5% CO2 for 70 hours. Lymphocyte proliferation was evaluated. Treatment of a DPP-4 inhibitor did not affect antigen-induced spleen-derived lymphocyte proliferation. *P < 0.05 vs. Myosin-, Linagliptin-, Bonferroni comparison test. Values are mean ± SEM.

Mentions: We performed a lymphocyte proliferation assay to examine the effect of a DPP-4 inhibitor on antigen-induced spleen cell proliferation (n = 12 per group). The DPP-4 inhibitor did not affect antigen-induced lymphocyte proliferation. (Fig. 3)


A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice.

Hirakawa H, Zempo H, Ogawa M, Watanabe R, Suzuki J, Akazawa H, Komuro I, Isobe M - PLoS ONE (2015)

Results of lymphocyte proliferation assay.Cultures with spleen-derived lymphocytes obtained from EAM mice were incubated at 37°C with 5% CO2 for 70 hours. Lymphocyte proliferation was evaluated. Treatment of a DPP-4 inhibitor did not affect antigen-induced spleen-derived lymphocyte proliferation. *P < 0.05 vs. Myosin-, Linagliptin-, Bonferroni comparison test. Values are mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359137&req=5

pone.0119360.g003: Results of lymphocyte proliferation assay.Cultures with spleen-derived lymphocytes obtained from EAM mice were incubated at 37°C with 5% CO2 for 70 hours. Lymphocyte proliferation was evaluated. Treatment of a DPP-4 inhibitor did not affect antigen-induced spleen-derived lymphocyte proliferation. *P < 0.05 vs. Myosin-, Linagliptin-, Bonferroni comparison test. Values are mean ± SEM.
Mentions: We performed a lymphocyte proliferation assay to examine the effect of a DPP-4 inhibitor on antigen-induced spleen cell proliferation (n = 12 per group). The DPP-4 inhibitor did not affect antigen-induced lymphocyte proliferation. (Fig. 3)

Bottom Line: No specific or effective treatment has been established.DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases.Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT
Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22). Pathological analysis revealed that the myocardial fibrosis area ratio in the treated group was significantly lower than in the untreated group. RT-PCR analysis demonstrated that the levels of mRNA expression of IL-2, TNF-α, IL-1β and IL-6 were significantly lower in the treated group than in the untreated group. Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation. Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents present in DPP-4 inhibitors may be useful to treat and/or prevent clinical myocarditis.

No MeSH data available.


Related in: MedlinePlus