PMC:7025476 / 13857-16312 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7025476","sourcedb":"PMC","sourceid":"7025476","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7025476","text":"OVA-Induced Activation of NLRP3 Inflammasome and Decrease of Melatonin Biosynthesis Are TLR2 Dependent\nWe next questioned how TLR2 regulated allergic airway inflammation. It has been shown that NLRP3 inflammasome is associated with allergic airway disease in response to OVA (10). We next assessed the link between TLR2 and NLRP3 inflammasome activity. Our results showed that NLRP3, cleaved form of IL-1β and caspase 1(p20) were increased in OVA-challenged WT mice in comparison with those of control mice, while such increase was completely abrogated in TLR2−/− mice following OVA challenge (Figures 3A–D). Similarly, productions of NLRP3-associated IL-1β and IL-18 were markedly decreased in OVA-challenged TLR2−/− mice, comparable to those of control mice (Figures 3E,F). Taken together, in this OVA model, NLRP3 inflammasome activated by OVA required licensing through TLR2, suggesting that TLR2-NLRP3 axis mediated OVA-allergic airway inflammation.\nFigure 3 OVA-induced activation of NLRP3 inflammasome and decrease of melatonin biosynthesis are TLR2 dependent. (A) NLRP3, mature IL-1β, pro-IL-1β, and caspase1(p20) western blot analysis. (B–D) Relative ratio of NLRP3 to GAPDH, IL-1β to pro-IL-1β, and caspase1(p20) to GAPDH. (E,F) ELISA analysis of IL-1β and IL-18 in BALF. (G) Western blot analysis of AANAT and ASMT in lung tissues. (H,I) Relative ratio of AANAT or ASMT to GAPDH. (J,K) The levels of 5-HT in BALF and melatonin in the lung homogenate were analyzed by ELISA. *p \u003c 0.05, **p \u003c 0.01, ***p \u003c 0.001. Consequently, we sought to investigate the regulatory networks how TLR2-NLRP3 axis mediated allergic airway diseases. Previous study has shown that TLR9 negatively regulates melatonin production in response to OVA challenge, and this endogenous synthesized melatonin may regulate airway inflammation (22). Here, our present study showed that OVA notably suppressed the protein expression of ASMT but not AANAT in lung tissues (Figures 3G–I), and lowered the level of 5-HT in BALF and melatonin in lung homogenate in WT mice (Figures 3J,K), while these reductions were significantly restored by TLR2 deficiency (Figures 3H–K). These data confirmed that besides TLR9, TLR2, another member of TLRs family suppressed endogenous melatonin biosynthesis in OVA-induced allergic airway inflammation, therefore suggesting that TLR2-NLRP3 -mediated allergic airway inflammation was associated with decreased endogenous melatonin biosynthesis.","divisions":[{"label":"title","span":{"begin":0,"end":102}},{"label":"p","span":{"begin":103,"end":954}},{"label":"figure","span":{"begin":955,"end":1522}},{"label":"label","span":{"begin":955,"end":963}},{"label":"caption","span":{"begin":965,"end":1522}},{"label":"p","span":{"begin":965,"end":1522}}],"tracks":[{"project":"TEST0","denotations":[{"id":"32117301-105-111-3829158","span":{"begin":276,"end":278},"obj":"[\"22323538\"]"},{"id":"32117301-183-189-3829159","span":{"begin":1824,"end":1826},"obj":"[\"26914888\"]"}],"attributes":[{"subj":"32117301-105-111-3829158","pred":"source","obj":"TEST0"},{"subj":"32117301-183-189-3829159","pred":"source","obj":"TEST0"}]},{"project":"2_test","denotations":[{"id":"32117301-22323538-35348483","span":{"begin":276,"end":278},"obj":"22323538"},{"id":"32117301-26914888-35348484","span":{"begin":1824,"end":1826},"obj":"26914888"}],"attributes":[{"subj":"32117301-22323538-35348483","pred":"source","obj":"2_test"},{"subj":"32117301-26914888-35348484","pred":"source","obj":"2_test"}]},{"project":"MyTest","denotations":[{"id":"32117301-22323538-35348483","span":{"begin":276,"end":278},"obj":"22323538"},{"id":"32117301-26914888-35348484","span":{"begin":1824,"end":1826},"obj":"26914888"}],"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":"32117301-22323538-35348483","pred":"source","obj":"MyTest"},{"subj":"32117301-26914888-35348484","pred":"source","obj":"MyTest"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST0","color":"#d8ec93","default":true},{"id":"2_test","color":"#e593ec"},{"id":"MyTest","color":"#93eccb"}]}]}}