Dopamine Controls Systemic Inflammation through Inhibition of NLRP3 Inflammasome

Yiqing Yan, Wei Jiang, Lei Liu, Xiaqiong Wang, Chen Ding, Zhigang Tian, and Rongbin Zhou1

Cell 160: 62–73, 2015

Speaker: Fu-Yu Chan (詹復宇)                            Time: 15:10~16:00

Commentator: Dr. Pin Ling (凌斌 老師)            Place: Room 601

Abstract:

Inflammasomes are involved in diverse inflammatory diseases. Therefore, the activation of inflammasomes needs to be tightly controlled to prevent excessive inflammation. However, the endogenous regulatory mechanisms of inflammasome activation are still unclear. Here, the authors reported that the neurotransmitter dopamine (DA) inhibits NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). DRD1 signaling negatively regulates NLRP3 inflammasome via a second messenger cyclic adenosine monophosphate (cAMP), which binds to NLRP3 and promotes its ubiquitination and degradation via the E3 ubiquitin ligase MARCH7. Importantly, in vivo data show that DA and DRD1 signaling prevent NLRP3 inflammasome-dependent inflammation, including neurotoxin-induced neuroinflammation, LPS-induced systemic inflammation, and monosodium urate crystal (MSU)-induced peritoneal inflammation. Taken together, these results reveal an endogenous mechanism of inflammasome regulation and suggest DRD1 as a potential target for the treatment of NLRP3 inflammasome-driven diseases.

References:

1. Basu, S., and Dasgupta, P.S. (2000). Dopamine, a neurotransmitter, influences the immune system. J. Neuroimmunol. 102, 113–124

2. Schmid-Burgk, J., Cavlar, T., and Hornung, V. (2011). Inflammasomes: current understanding and open questions. Cell. Mol. Life Sci. 68, 765–783.