Immunopharmacology and immunotoxicology · 2025
Adenosine A2B receptor mediates cyclosporine counteraction of inflammatory and renal consequences of sepsis in rats.
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Salama Simone A, Sallam Marwa Y, El-Gowilly Sahar M
Аннотация
INTRODUCTION: The immunosuppressant drug cyclosporine A (CsA) demonstrates anti-inflammatory properties in numerous pathological conditions. It acts through modulating T-cell receptor signaling, reducing the expression of inflammatory cytokines, and inhibiting mitochondrial permeability, besides modulating vascular response. These features make it a potential drug to prevent or treat septic acute kidney injury (AKI).
OBJECTIVE: In this study, we investigated whether CsA exerts a protective effect against hemodynamic, inflammatory, and renovascular consequences of sepsis and whether these effects are modulated by adenosine receptor signaling.
MATERIAL AND METHODS: Cecal ligation and puncture (CLP) was utilized to induce sepsis 24 h before hemodynamic and renovascular studies were implicated. Renal vasoconstrictions and vasodilatations were induced by cumulative bolus injections of phenylephrine (PE, 0.41-900 ng) and acetylcholine (ACh, 0.01-7.29 nmol), respectively.
RESULTS: The data showed that CsA abrogated CLP-evoked hypotension, tachycardia, and impaired renovascular responsiveness. Similarly, the elevation in kidney biomarkers together with the pro-inflammatory cytokines (Tumor necrosis factor-alpha (TNFα) and Interleukin-6 (IL-6)) were also blunted after CsA administration. Likewise, the elevation in nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and decrease in A2BRs renal tubular expression in sepsis was reversed in CsA-treated rats. These advantageous effects of CsA disappeared upon concurrent exposure to the selective A2BR antagonist, Alloxazine.
CONCLUSION: These results suggest a key role for functional A2BR in CsA counteracting CLP-induced hemodynamic, inflammatory, and renal dysfunction in rats.
OBJECTIVE: In this study, we investigated whether CsA exerts a protective effect against hemodynamic, inflammatory, and renovascular consequences of sepsis and whether these effects are modulated by adenosine receptor signaling.
MATERIAL AND METHODS: Cecal ligation and puncture (CLP) was utilized to induce sepsis 24 h before hemodynamic and renovascular studies were implicated. Renal vasoconstrictions and vasodilatations were induced by cumulative bolus injections of phenylephrine (PE, 0.41-900 ng) and acetylcholine (ACh, 0.01-7.29 nmol), respectively.
RESULTS: The data showed that CsA abrogated CLP-evoked hypotension, tachycardia, and impaired renovascular responsiveness. Similarly, the elevation in kidney biomarkers together with the pro-inflammatory cytokines (Tumor necrosis factor-alpha (TNFα) and Interleukin-6 (IL-6)) were also blunted after CsA administration. Likewise, the elevation in nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and decrease in A2BRs renal tubular expression in sepsis was reversed in CsA-treated rats. These advantageous effects of CsA disappeared upon concurrent exposure to the selective A2BR antagonist, Alloxazine.
CONCLUSION: These results suggest a key role for functional A2BR in CsA counteracting CLP-induced hemodynamic, inflammatory, and renal dysfunction in rats.