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[Intervention effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice].
Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Sep; 40(5):817-20, 825.SD

Abstract

OBJECTIVE

To investigate the therapeutic effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice.

METHODS

BALB/c mice were randomly divided into three groups, AS605240 group and vehicle group were injected subcutaneously with emulsions containing CFA and 100 ng peptide which derived from murine cardiac alpha-myosin heavy chain on day 0 and 7 while control group were injected with emulsions containing CFA and PBS. AS605240 group received the oral administration of AS605240 50 mg/(kg x d). The vehicle group received the oral administration of an equal volume of 0.5% carboxymethylcellulose. 21 days after the first immunization, mice were sacrificed, heart and body weight were measured. Myocarditis severity was evaluated according to a semi-quantitative scoring system in heart sections. Immunohistochemistry was performed to determine the effect of AS605240 on myocardium macrophage infiltration; TNF-alpha levels in myocardium were determined by ELISA. In vitro and in vivo chemotaxis assays were performed to determine the effect of AS605240 on MCP-1-induced macrophage chemotaxis.

RESULTS

Histological examination of the heart showed that AS605240 significantly relieved the murine myocarditis and reduced heart/body weight ratios in experimental autoimmune myocarditis (EAM) (P< 0.01). Immunohistochemical detection showed that AS605240 significantly suppressed macrophage infiltration into the heart with EAM. ELISA demonstrated that AS605240 down-regulated TNF-alpha levels in myocardium (P<0.01). In vitro and in vivo chemotaxis assays indicated that AS605240 significantly suppressed MCP-1-induced macrophage chemotaxis (P<0.01).

CONCLUSION

AS605240 may be an effective drug for autoimmune myocarditis, of which the mechanism is relating to suppress macrophage chemotaxis and macrophage infiltration into myocardium, and to decrease TNF-alpha levels in myocardium.

Authors+Show Affiliations

State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

19950590

Citation

Jin, Ke, et al. "[Intervention Effect of PI3Kgamma Inhibitor AS605240 On Autoimmune Myocarditis in Mice]." Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition, vol. 40, no. 5, 2009, pp. 817-20, 825.
Jin K, Song LF, He CM, et al. [Intervention effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009;40(5):817-20, 825.
Jin, K., Song, L. F., He, C. M., Wang, Z. L., Hu, X. H., & Wu, X. H. (2009). [Intervention effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice]. Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition, 40(5), 817-20, 825.
Jin K, et al. [Intervention Effect of PI3Kgamma Inhibitor AS605240 On Autoimmune Myocarditis in Mice]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009;40(5):817-20, 825. PubMed PMID: 19950590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Intervention effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice]. AU - Jin,Ke, AU - Song,Li-Fang, AU - He,Chun-Mei, AU - Wang,Zhen-Ling, AU - Hu,Xiao-Hong, AU - Wu,Xiao-Hua, PY - 2009/12/3/entrez PY - 2009/12/3/pubmed PY - 2010/4/28/medline SP - 817-20, 825 JF - Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition JO - Sichuan Da Xue Xue Bao Yi Xue Ban VL - 40 IS - 5 N2 - OBJECTIVE: To investigate the therapeutic effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice. METHODS: BALB/c mice were randomly divided into three groups, AS605240 group and vehicle group were injected subcutaneously with emulsions containing CFA and 100 ng peptide which derived from murine cardiac alpha-myosin heavy chain on day 0 and 7 while control group were injected with emulsions containing CFA and PBS. AS605240 group received the oral administration of AS605240 50 mg/(kg x d). The vehicle group received the oral administration of an equal volume of 0.5% carboxymethylcellulose. 21 days after the first immunization, mice were sacrificed, heart and body weight were measured. Myocarditis severity was evaluated according to a semi-quantitative scoring system in heart sections. Immunohistochemistry was performed to determine the effect of AS605240 on myocardium macrophage infiltration; TNF-alpha levels in myocardium were determined by ELISA. In vitro and in vivo chemotaxis assays were performed to determine the effect of AS605240 on MCP-1-induced macrophage chemotaxis. RESULTS: Histological examination of the heart showed that AS605240 significantly relieved the murine myocarditis and reduced heart/body weight ratios in experimental autoimmune myocarditis (EAM) (P< 0.01). Immunohistochemical detection showed that AS605240 significantly suppressed macrophage infiltration into the heart with EAM. ELISA demonstrated that AS605240 down-regulated TNF-alpha levels in myocardium (P<0.01). In vitro and in vivo chemotaxis assays indicated that AS605240 significantly suppressed MCP-1-induced macrophage chemotaxis (P<0.01). CONCLUSION: AS605240 may be an effective drug for autoimmune myocarditis, of which the mechanism is relating to suppress macrophage chemotaxis and macrophage infiltration into myocardium, and to decrease TNF-alpha levels in myocardium. SN - 1672-173X UR - https://www.unboundmedicine.com/medline/citation/19950590/[Intervention_effect_of_PI3Kgamma_inhibitor_AS605240_on_autoimmune_myocarditis_in_mice]_ L2 - https://medlineplus.gov/autoimmunediseases.html DB - PRIME DP - Unbound Medicine ER -