A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence.
A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence.
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幽门螺杆菌会导致终生感染，并提供细菌适应和持续定植的模型。腺苷是一种抗炎介质，可限制炎症期间的组织损伤。我们研究了腺苷在 T 细胞介导的胃炎和细菌持久性调节中的作用。激活 4 小时后，人类 T 辅助 (Th) 细胞增加了 A2A 腺苷受体 (A2AAR) mRNA 水平（七倍）。 A2AAR 是在静息和刺激的胃或外周 Th 细胞中表达的主要亚型。使用 A2AAR 激动剂 ATL313 进行刺激，可增加环 AMP (cAMP) 的积累，并使白细胞介素 2 (IL-2) 的产生减少 20-50%。 ATL313 还可以减弱肿瘤坏死因子-α (TNF-α) 和干扰素-γ (IFN-γ) 的产生，而这种作用可被 A2AAR 拮抗剂抑制。 IL-10缺陷型小鼠的幽门螺杆菌感染由于明显的炎症而被自发清除。感染期间施用 ATL313 可减少胃炎和促炎细胞因子反应，同时细菌负荷增加。相反，A2AAR 缺陷小鼠的感染会加剧胃炎。因此，A2AAR 限制了 Th 细胞的促炎作用，有利于慢性螺杆菌感染。
Helicobacter pylori causes a lifelong infection and provides a model of bacterial adaptation and persistent colonization. Adenosine is an anti-inflammatory mediator that limits tissue damage during inflammation. We studied the role of adenosine in the T-cell-mediated regulation of gastritis and bacterial persistence. After 4h of activation, human T helper (Th) cells increased A2A adenosine receptor (A2AAR) mRNA level (sevenfold). A2AAR was the predominant subtype expressed in resting and stimulated gastric or peripheral Th cells. Stimulation with ATL313, an A2AAR agonist, increased cyclic AMP (cAMP) accumulation and reduced interleukin-2 (IL-2) production by 20–50%. ATL313 also attenuated tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production, which was inhibited by an A2AAR antagonist. Infection of IL-10-deficient mice with H. pylori is cleared spontaneously due to the marked inflammation. Administration of ATL313 during infection reduced gastritis and pro-inflammatory cytokine responses while bacterial load increased. In contrast, infection of A2AAR-deficient mice enhanced gastritis. Thus, A2AAR limits the pro-inflammatory effects of Th cells and favor chronic Helicobacter infection.
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20.3
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