2016 Fiscal Year Final Research Report
Combination therapy of beta2 -adrenoceptor activation and steroids for sepsis-induced renal injury
| Project/Area Number |
25462832
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Research Collaborator |
KUROSAKI Kumiko
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | 敗血症 / 腎傷害 / β２アドレナリン受容体 / グルココルチコイド / TNF-α / ヒストン |
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| Outline of Final Research Achievements |
This study was undertaken to explore whether cross-talk between β2-adrenoceptor(β2-AR) and glucocorticoid may produce additive or even synergic anti-inflammatory effects, resulting in kidney protection against sepsis-induced acute kidney injury(AKI). Results demonstrated that administration of glucocorticoid in the kidney and renal cells with over-expression of β2-AR appeared to modulate renal dysfunction and inflammation following sepsis by altering cAMP-PKA, cannabinoid-1 and CD14-TLR4-TNF-α pathways. In addition, the combination therapy produced modulation of systemic nitric oxide and angiotensin II, and renal histone-modifying enzymes(HAT, HDAC, H3K9Ac）, which further suppressed renal TNF-α gene transcription. Moreover, the combination therapy improved the survival of the rats exposed to sepsis-induced AKI. From these findings, the effect of β2-AR activation on glucocorticoid actions via TNF-α pathways was a critical effector in the host defense against sepsis-induced AKI.
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| Free Research Field |
小児科学
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