Bee Venom Inhibits Porphyromonas gingivalis Lipopolysaccharides-Induced Pro-Inflammatory Cytokines through Suppression of NF-κB and AP-1 Signaling Pathways.
Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues.Porphyromonas gingivalis(P. gingivalis), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine for various diseases. Previous studies have demonstrated the anti-inflammatory, anti-bacterial effects of BV. However, a direct role and cellular mechanism of BV on periodontitis-like human keratinocytes have not been explored. Therefore, we investigated the anti-inflammatory mechanism of BV againstP. gingivalisLPS (PgLPS)-induced HaCaT human keratinocyte cell line. The anti-inflammatory effect of BV was demonstrated by various molecular biological methods. The results showed that PgLPS increased the expression of Toll-like receptor (TLR)-4 and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and interferon (IFN)-γ. In addition, PgLPS induced activation of the signaling pathways of inflammatory cytokines-related transcription factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). BV effectively inhibited those pro-inflammatory cytokines through suppression of NF-κB and AP-1 signaling pathways. These results suggest that administration of BV attenuates PgLPS-induced inflammatory responses. Furthermore, BV may be a useful treatment to anti-inflammatory therapy for periodontitis.
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. kimwoonhae@cu.ac.kr.
Woon-Hae
WH
Kim
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. ahj119@cu.ac.kr.
Hyun-Jin
HJ
An
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. jy1118@cu.ac.kr.
Jung-Yeon
JY
Kim
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. daldy99@naver.com.
Mi-Gyeong
MG
Gwon
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. asdf8760@naver.com.
Hyemin
H
Gu
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. jbpark@cu.ac.kr.
Jae-Bok
JB
Park
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. wjsung@cu.ac.kr.
Woo Jung
WJ
Sung
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. kyc1855@hanmail.net.
Yong-Chul
YC
Kwon
Department of Dermatology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. gdpk1217@naver.com.
Kyung-Duck
KD
Park
Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, 300, Nongsaengmyeong-ro, Wansan-gu, Jeonju-si 54875, Korea. sangmih@korea.kr.
Sang Mi
SM
Han
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. kkparkl@cu.ac.kr.
Kwan-Kyu
KK
Park
D001514:Bee Venoms / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D016966:Porphyromonas gingivalis / Q000737:chemistry*; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D001514:Bee Venoms; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011135:Polysaccharides, Bacterial; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
Porphyromonas gingivalis; bee venom; lipopolysaccharides; periodontitis