Adenosine A(2A) receptor, a potential valuable target for controlling reoxygenated DCs-triggered inflammation

作者：Liu, Chunmei; Shang, Qianwen; Bai, Yang; Guo, Chun; Zhu, Faliang; Zhang, Lining; Wang, Qun^*

来源：Molecular Immunology, 2015, 63(2): 559-565.

DOI：10.1016/j.molimm.2014.10.012

• Reoxygenation
• Dendritic cells
• Adenosine receptor
• Inflammation
• Hypoxia

Dendritic cells (DCs) exposed to various oxygen tensions under physiopathological conditions are the critical immune cells linking innate and adaptive immunity. We have previously demonstrated that reoxygenation of hypoxia-differentiated DCs triggers complete DCs activation and inflammatory responses, so restraining the activation of reoxygenated DCs is important to suppress inflammatory responses in diseases caused by oxygen redelivery such as ischemia-reperfusion injury. In the current study, we showed that reoxygenation of hypoxia-differentiated DCs led to predominant expression of high levels of adenosine receptor A(2A)R on reoxygenated DCs as compared to those on hypoxic or normoxic DCs. Agonist CGS21680 targeting A(2A)R could effectively inhibit the maturation and activation of reoxygenated DCs through downregulating the expression of MHC class II molecules and CD86. In response to CGS21680 treatment, reoxygenated DCs exhibited a decrease in proinflammatory cytokines IL-1 beta, IL-6 and TNF-alpha, and an increase in immune-regulatory cytokine TGF-beta. These data suggest the critical role of A(2A)R signaling pathway in inhibiting the maturation and proinflammatory function of reoxygenated DCs, thereby proposing A(2A)R as a potential valuable target for controlling reoxygenated DCs-triggered inflammation.

• 出版日期2015-2
• 单位山东大学; 山东省立医院