Aimin Liu1, Shifang Ding2. 1. Department of Intensive Care Unit, Qilu Hospital, Shandong University, Shandong Province, China. 2. Department of Intensive Care Unit, Qilu Hospital, Shandong University, Shandong Province, China Dingshifang123@aliyun.com.
Abstract
OBJECTIVE: Dopamine (DA) is a neurotransmitter and chemical mediator, and DA receptors (particularly DRD1) are present on the majority of immune cells. The aim of this study was to investigate the effects of DA on lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW264.7 cells. METHODS: Cells were exposed to DA (10*-3, 10*-4 and 10*-5M) for 2 hr prior, with or without LPS (1μg/ml) for 6hr. Additionally, DA and NLRP3 inhibitor, MCC950 had treated LPS-stimulated RAW264.7 cells. CCK8 assays were used for the assessment of cell viability and Quantitative real-time PCR (qRT-PCR) and western blot analysis were used to examine mRNA and protein expression levels, respectively. RESULTS: Our results reveal that DA reduces the mRNA and protein expression of tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6) and interleukin (1L), (IL-1β) in RAW 264.7 cells stimulated with LPS. DA also inhibited the mRNA and protein expression levels of nitric oxide synthase (iNOS) and downregulated NLRP3 and caspase-1 expression. The administration of DA and NLRP3 inhibitor, MCC950 played a synergistic role in suppressing NLRP3 activity. CONCLUSION: Taken together, these findings demonstrate that DA displays potent anti-inflammatory effects that are mediated by the suppression of pro-inflammatory mediators (IL-1β, IL-6, TNF-α), cytokines (iNOS) and the NLRP3 inflammasome activation. Improvement of DA correlated with its effect on NLRP3 activation. Thus, DA and agonists of DRD1, as a functional molecule that bridges the neuronal and immune systems, may represent effective strategies for limiting pathological inflammation.
OBJECTIVE:Dopamine (DA) is a neurotransmitter and chemical mediator, and DA receptors (particularly DRD1) are present on the majority of immune cells. The aim of this study was to investigate the effects of DA on lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW264.7 cells. METHODS: Cells were exposed to DA (10*-3, 10*-4 and 10*-5M) for 2 hr prior, with or without LPS (1μg/ml) for 6hr. Additionally, DA and NLRP3 inhibitor, MCC950 had treated LPS-stimulated RAW264.7 cells. CCK8 assays were used for the assessment of cell viability and Quantitative real-time PCR (qRT-PCR) and western blot analysis were used to examine mRNA and protein expression levels, respectively. RESULTS: Our results reveal that DA reduces the mRNA and protein expression of tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6) and interleukin (1L), (IL-1β) in RAW 264.7 cells stimulated with LPS. DA also inhibited the mRNA and protein expression levels of nitric oxide synthase (iNOS) and downregulated NLRP3 and caspase-1 expression. The administration of DA and NLRP3 inhibitor, MCC950 played a synergistic role in suppressing NLRP3 activity. CONCLUSION: Taken together, these findings demonstrate that DA displays potent anti-inflammatory effects that are mediated by the suppression of pro-inflammatory mediators (IL-1β, IL-6, TNF-α), cytokines (iNOS) and the NLRP3 inflammasome activation. Improvement of DA correlated with its effect on NLRP3 activation. Thus, DA and agonists of DRD1, as a functional molecule that bridges the neuronal and immune systems, may represent effective strategies for limiting pathological inflammation.
Authors: Anthony H Cincotta; Eugenio Cersosimo; Mariam Alatrach; Michael Ezrokhi; Christina Agyin; John Adams; Robert Chilton; Curtis Triplitt; Bindu Chamarthi; Nicholas Cominos; Ralph A DeFronzo Journal: Int J Mol Sci Date: 2022-08-09 Impact factor: 6.208