Baicalin Downregulates Porphyromonas gingivalis Lipopolysaccharide-Upregulated IL-6 and IL-8 Expression in Human Oral Keratinocytes by Negative Regulation of TLR Signaling.docVIP

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Baicalin Downregulates Porphyromonas gingivalis Lipopolysaccharide-Upregulated IL-6 and IL-8 Expression in Human Oral Keratinocytes by Negative Regulation of TLR Signaling.doc

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Baicalin Downregulates Porphyromonas gingivalis Lipopolysaccharide-Upregulated IL-6 and IL-8 Expression in Human Oral Keratinocytes by Negative Regulation of TLR Signaling

BaicalinDownregulatesPorphyromonasgingivalis Lipopolysaccharide-UpregulatedIL-6andIL-8Expression inHumanOralKeratinocytesbyNegativeRegulationof TLRSignaling WeiLuo1,Cun-YuWang2,LijianJin1* 1FacultyofDentistry,TheUniversityofHongKong,HongKongSAR,China,2UniversityofCaliforniaLosAngeles,SchoolofDentistry,LosAngeles,California,United StatesofAmerica Abstract Periodontal(gum)diseaseisoneofthemainglobaloralhealthburdensandsevereperiodontaldisease(periodontitis)isa leading cause of tooth loss in adults globally. It also increases the risk of cardiovascular disease and diabetes mellitus. Porphyromonas gingivalis lipopolysaccharide (LPS) is a key virulent attribute that significantly contributes to periodontal pathogenesis. Baicalin is a flavonoid from Scutellaria radix, an herb commonly used in traditional Chinese medicine for treatinginflammatorydiseases.ThepresentstudyexaminedthemodulatoryeffectofbaicalinonP.gingivalisLPS-induced expressionofIL-6andIL-8inhumanoralkeratinocytes(HOKs).Cellswerepre-treatedwithbaicalin(0–80 mM)for24h,and subsequentlytreatedwithP.gingivalisLPSat10mg/mlwithorwithoutbaicalinfor3h.IL-6andIL-8transcriptsandproteins were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of nuclear factor-kB (NF-kB), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) proteinswasanalyzedbywesternblot.Apanelofgenesrelatedtotoll-likereceptor(TLR)signalingwasexaminedbyPCR array. We found that baicalin significantly downregulated P. gingivalis LPS-stimulated expression of IL-6 and IL-8, and inhibitedP.gingivalisLPS-activatedNF-kB,p38MAPKandJNK.Furthermore,baicalinmarkedlydownregulatedP.gingivalis LPS-inducedexpressionofgenesassociatedwithTLRsignaling.Inconclusion,thepresentstudyshowsthatbaicalinmay significantlydownregulateP.gingivalisLPS-upregulatedexpressionofIL-6andIL-8inHOKsvianegativeregulationofTLR signaling. Citation:LuoW,WangC-Y,JinL(2012)BaicalinDownregulatesPor