Withaferin A inhibits inflammatory responses induced by Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans in macrophages

• Published in: Molecular medicine reports Vol. 14; no. 1; pp. 983 - 988
• Main Authors: NOH, EUI-JEONG, KANG, MING-JUNG, JEONG, YU-JIN, LEE, JUN-YOUNG, PARK, JUNG-HWAN, CHOI, HYE-JIN, OH, SANG-MUK, LEE, KYUNG-BOK, KIM, DONG-JAE, SHIN, JI-AE, CHO, SUNG-DAE, PARK, JONG-HWAN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.07.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Aggregatibacter actinomycetemcomitans; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Bacteria; Bacterial infections; Bone marrow; c-Jun protein; Care and treatment; Cell culture; Cytokines; Cytokines - metabolism; Development and progression; Disease Models, Animal; Fusobacterium Infections - drug therapy; Fusobacterium Infections - immunology; Fusobacterium Infections - metabolism; Fusobacterium Infections - microbiology; Fusobacterium nucleatum; Gene Expression; Health aspects; Immune response; Infections; inflammation; JNK protein; Laboratories; Macrophages; Macrophages - drug effects; Macrophages - microbiology; Macrophages - physiology; Male; Mice; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Observations; Pasteurellaceae Infections - drug therapy; Pasteurellaceae Infections - immunology; Pasteurellaceae Infections - metabolism; Pasteurellaceae Infections - microbiology; Periodontitis; Periodontitis - drug therapy; Periodontitis - immunology; Periodontitis - metabolism; Periodontitis - microbiology; Phosphorylation; Plant metabolites; Proteins; Teeth; TLR2 protein; TLR4 protein; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4; Toll-like receptors; Transcription factors; Tumor necrosis factor; Tumor necrosis factor-TNF; Withaferin A; Withanolides - pharmacology; United States > US
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2016.5326

Periodontitis is a progressive chronic inflammatory disease and a major cause of tooth loss in humans. As a withanolides, withaferin A (WA) is known to exhibit strong anti-inflammatory activity. The present study examined whether WA inhibited inflammatory responses in macrophages in response to two representative periodontal pathogens, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans. Murine bone marrow-derived macrophages (BMDMs) were used in this study and cytokine production in culture supernatants was measured by enzyme-linked immunosorbent assays. Western blot analysis was performed to determine the activation of nuclear factor-κB and mitogen-activated protein kinases (MAPKs) and the expression of inducible nitric oxide synthase (iNOS), toll-like receptor (TLR) 2 and TLR4. The production of nitric oxide (NO) was determined by the Griess reaction. WA treatment was shown to decrease interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in BMDMs in response to F. nucleatum and A. actinomycetemcomitans in a dose-dependent manner. The phosphorylation of IκB-α and MAPKs (p38, extracellular signal-regulated kinases and c-Jun N-terminal kinases) induced by F. nucleatum and A. actinomycetemcomitans was also inhibited by WA. F. nucleatum and A. actinomycetemcomitans induced iNOS expression and NO production in BMDMs, which was inhibited by WA in a dose-dependent manner. WA also reduced endogenous and induced expression of TLR2 and TLR4 in these cells. These results suggest that WA may be a potential therapeutic agent or preventive additive for periodontitis control.