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|
| Type |
Poster Presentation |
| Area |
Life Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 19일 (금요일) 11:00~12:30 |
| Code |
LIFE.P-368 |
| Subject |
Natural TLR2 antagonist phloretin suppresses TLR2-mediated Inflammation |
| Authors |
Jieun Kim, Yangmee Kim*
Department of Biotechnology, Konkuk University, Korea
|
| Abstract |
Phloretin is a naturally occurring dietary flavonoid that is abundant in fruit. Here, we investigated whether the anti-inflammatory activity of phloretin is mediated through TLR2 pathways, and whether phloretin acts as an inhibitor of TLR2/1 heterodimerization. We tested the effects of phloretin on TNF-α production induced by various TLR-specific agonists. Phloretin significantly inhibited Pam3CSK4-induced signaling in Raw264.7 cells compared to TLR signaling induced by the other agonists tested. We further tested the effects of phloretin in HEK293-hTLR2 cells induced by Pam3CSK4, and confirmed that phloretin has comparable inhibition of TLR2/1 heterodimerization. Moreover, phloretin reduced the secretion of the inflammatory cytokines TNF-α and IL-8, whereas it did not significantly reduce these cytokines in cells. Western blot results showed that phloretin significantly suppressed Pam3CSK4-induced and NF-κB p65 expression. The molecular interactions between phloretin and TLR2 were investigated using bio-layer interferometry and in silico docking. Phloretin bound with micromolar binding affinity, and we proposed a binding model of phloretin at the TLR2–TLR1 interface. Overall, we confirmed that phloretin inhibits the heterodimerization of TLR2/1, highlighting TLR2 signaling as a therapeutic target for treating TLR2-mediated inflammatory immune diseases. |
| E-mail |
za3524@konkuk.ac.kr |
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123rd General Meeting of the KCS