PMC:7025476 / 29900-31505
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7025476","sourcedb":"PMC","sourceid":"7025476","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7025476","text":"Among the three melatonin receptors, the anti-inflammatory effect of melatonin is reported to be mainly mediated by MT2 melatonin receptor (61). Luzindole is considered as a non-selective MT1/MT2 receptor antagonist, showing 15–26 times higher affinity for MT2 receptor, which pharmacologically blocks the effect of melatonin (62). Therefore, luzindole was used as indicated (28) to further confirm that melatonin elicited its effect on NLRP3 inflammasome activity via TLR2 signal. Our results showed that although administration of luzindole to OVA-challenged TLR2−/− mice significantly reduced the expression of melatonin synthetase AANAT and ASMT, and subsequent level of melatonin, it exhibited null effects on the level of 5-HT in BALF, OVA-induced leukocyte infiltration, the level of IgE, Th2 cytokines production, and NLRP3 inflammasome activity, it only aggravated allergen-induced mucus hyper-secretion. To our knowledge, this is the first study showing that luzindole inhibited lung melatonin synthesis, which may be due to the blockage of 5-HT conversion to melatonin. These combined data suggested that the effect of melatonin on airway inflammation and NLRP3 inflammasome activity requires TLR2 signaling, and melatonin which is modulated by TLR2 signal feedback regulates TLR2 signaling, and subsequently regulates NLRP3 inflammasome activity and airway inflammation. However, the inhibitory effect of melatonin on airway remodeling characterized by mucus hyper-secretion may not require TLR2 signal, because luzindole still deteriorates mucus production even in the absence of TLR2 signal.","tracks":[{"project":"TEST0","denotations":[{"id":"32117301-140-146-3829206","span":{"begin":140,"end":142},"obj":"[\"16217123\"]"},{"id":"32117301-182-188-3829207","span":{"begin":327,"end":329},"obj":"[\"2843633\"]"}],"attributes":[{"subj":"32117301-140-146-3829206","pred":"source","obj":"TEST0"},{"subj":"32117301-182-188-3829207","pred":"source","obj":"TEST0"}]},{"project":"2_test","denotations":[{"id":"32117301-16217123-35348531","span":{"begin":140,"end":142},"obj":"16217123"},{"id":"32117301-2843633-35348532","span":{"begin":327,"end":329},"obj":"2843633"}],"attributes":[{"subj":"32117301-16217123-35348531","pred":"source","obj":"2_test"},{"subj":"32117301-2843633-35348532","pred":"source","obj":"2_test"}]},{"project":"MyTest","denotations":[{"id":"32117301-16217123-35348531","span":{"begin":140,"end":142},"obj":"16217123"},{"id":"32117301-2843633-35348532","span":{"begin":327,"end":329},"obj":"2843633"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"32117301-16217123-35348531","pred":"source","obj":"MyTest"},{"subj":"32117301-2843633-35348532","pred":"source","obj":"MyTest"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST0","color":"#9793ec","default":true},{"id":"2_test","color":"#a8ec93"},{"id":"MyTest","color":"#ec93c2"}]}]}}