PMID- 27220676
OWN - NLM
STAT- MEDLINE
DCOM- 20170406
LR  - 20170406
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 14
IP  - 1
DP  - 2016 Jul
TI  - Withaferin A inhibits inflammatory responses induced by Fusobacterium nucleatum 
      and Aggregatibacter actinomycetemcomitans in macrophages.
PG  - 983-8
LID - 10.3892/mmr.2016.5326 [doi]
AB  - 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‑kappaB 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)‑alpha production in BMDMs in 
      response to F. nucleatum and A. actinomycetemcomitans in a dose‑dependent manner. 
      The phosphorylation of IkappaB‑alpha 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.
FAU - Noh, Eui-Jeong
AU  - Noh EJ
AD  - Department of Biochemistry, College of Medicine, Konyang University, Daejeon 
      302‑718, Republic of Korea.
FAU - Kang, Ming-Jung
AU  - Kang MJ
AD  - Laboratory of Animal Medicine, College of Veterinary Medicine and BK21 Project 
      Team, Chonnam National University, Gwangju 500‑757, Republic of Korea.
FAU - Jeong, Yu-Jin
AU  - Jeong YJ
AD  - Department of Biochemistry, College of Medicine, Konyang University, Daejeon 
      302‑718, Republic of Korea.
FAU - Lee, Jun-Young
AU  - Lee JY
AD  - Laboratory of Animal Medicine, College of Veterinary Medicine and BK21 Project 
      Team, Chonnam National University, Gwangju 500‑757, Republic of Korea.
FAU - Park, Jung-Hwan
AU  - Park JH
AD  - Department of Biochemistry, College of Medicine, Konyang University, Daejeon 
      302‑718, Republic of Korea.
FAU - Choi, Hye-Jin
AU  - Choi HJ
AD  - Department of Biochemistry, College of Medicine, Konyang University, Daejeon 
      302‑718, Republic of Korea.
FAU - Oh, Sang-Muk
AU  - Oh SM
AD  - Department of Biochemistry, College of Medicine, Konyang University, Daejeon 
      302‑718, Republic of Korea.
FAU - Lee, Kyung-Bok
AU  - Lee KB
AD  - Department of Biochemistry, College of Medicine, Konyang University, Daejeon 
      302‑718, Republic of Korea.
FAU - Kim, Dong-Jae
AU  - Kim DJ
AD  - Department of Biochemistry, College of Medicine, Konyang University, Daejeon 
      302‑718, Republic of Korea.
FAU - Shin, Ji-Ae
AU  - Shin JA
AD  - Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience, 
      Chonbuk National University, Jeonju, North Jeolla 561‑756, Republic of Korea.
FAU - Cho, Sung-Dae
AU  - Cho SD
AD  - Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience, 
      Chonbuk National University, Jeonju, North Jeolla 561‑756, Republic of Korea.
FAU - Park, Jong-Hwan
AU  - Park JH
AD  - Laboratory of Animal Medicine, College of Veterinary Medicine and BK21 Project 
      Team, Chonnam National University, Gwangju 500‑757, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20160523
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Withanolides)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - L6DO3QW4K5 (withaferin A)
SB  - IM
MH  - *Aggregatibacter actinomycetemcomitans
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Fusobacterium Infections/drug therapy/*immunology/metabolism/*microbiology
MH  - *Fusobacterium nucleatum
MH  - Gene Expression
MH  - Macrophages/*drug effects/microbiology/*physiology
MH  - Male
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Pasteurellaceae Infections/drug therapy/*immunology/metabolism/*microbiology
MH  - Periodontitis/drug therapy/immunology/metabolism/microbiology
MH  - Toll-Like Receptor 2/metabolism
MH  - Toll-Like Receptor 4
MH  - Withanolides/*pharmacology
EDAT- 2016/05/26 06:00
MHDA- 2017/04/07 06:00
CRDT- 2016/05/26 06:00
PHST- 2015/03/23 00:00 [received]
PHST- 2016/04/26 00:00 [accepted]
PHST- 2016/05/26 06:00 [entrez]
PHST- 2016/05/26 06:00 [pubmed]
PHST- 2017/04/07 06:00 [medline]
AID - 10.3892/mmr.2016.5326 [doi]
PST - ppublish
SO  - Mol Med Rep. 2016 Jul;14(1):983-8. doi: 10.3892/mmr.2016.5326. Epub 2016 May 23.