Tropisetron attenuates lipopolysaccharide induced neuroinflammation by inhibiting NF-κB and SP/NK1R signaling pathway

Journal of Neuroimmunology
Yan YuGuangchun Sun

Abstract

Tropisetron, an antagonist of serotonin type 3 receptors (5-HT3Rs), has been investigated in colonic inflammatory process. Since substance P/neurokinin 1 receptor (SP/NK1R) signaling pathway plays a key role in several sensory neuronal inflammatory. We evaluated the anti-inflammatory activity of tropisetron in mice cerebral cortex, and discovered that it was a potential inhibitor in LPS-mediated neuron inflammation through SP/NK1R signaling pathway. We found that tropisetron significantly reduced the increased number of iba-1 positive microglia, down-regulated the gene transcription and protein expression of IL-1β,IL-6 and TNF-α in LPS stimulated cerebral cortex. To characterize the inhibitory mechanism of tropisetron at the SP response in inflammation, we further examined the effect of tropisetron on NF-κB and SP/NK1R signaling pathway in the process of mice cerebral cortex inflammation. We found that tropisetron inhibited the gene transcription and protein expression of NF-κB, SP, NK1R via inhibiting 5-HT3R activity. These findings might provide new insights into the anti-inflammatory activities of 5-HT3R inhibitor tropisetron, which would be the interaction of serotonin receptor signaling and SP/NK1R pathway. These might hig...Continue Reading

Citations

Aug 17, 2020·Neurochemical Research·Ashkan DivanbeigiMohammad-Reza Zarrindast
Mar 24, 2021·Multiple Sclerosis and Related Disorders·Mikhail MelnikovAlexey Boykо

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