PMID- 25791329
OWN - NLM
STAT- MEDLINE
DCOM- 20160211
LR  - 20221207
IS  - 1879-1506 (Electronic)
IS  - 0003-9969 (Linking)
VI  - 60
IP  - 6
DP  - 2015 Jun
TI  - Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins 
      act in synergy with cathelicidin (LL-37) to reduce the LPS-induced inflammatory 
      response in a three-dimensional co-culture model of gingival epithelial cells and 
      fibroblasts.
PG  - 845-53
LID - S0003-9969(15)00049-7 [pii]
LID - 10.1016/j.archoralbio.2015.02.021 [doi]
AB  - OBJECTIVES: The human antimicrobial peptide cathelicidin (LL-37) possesses 
      anti-inflammatory properties that may contribute to attenuating the inflammatory 
      process associated with chronic periodontitis. Plant polyphenols, including those 
      from cranberry and green tea, have been reported to reduce inflammatory cytokine 
      secretion by host cells. In the present study, we hypothesized that A-type 
      cranberry proanthocyanidins (AC-PACs) and green tea epigallocatechin-3-gallate 
      (EGCG) act in synergy with LL-37 to reduce the secretion of inflammatory 
      mediators by oral mucosal cells. METHODS: A three-dimensional (3D) co-culture 
      model of gingival epithelial cells and fibroblasts treated with non-cytotoxic 
      concentrations of AC-PACs (25 and 50 mug/ml), EGCG (1 and 5 mug/ml), and LL-37 (0.1 
      and 0.2 muM) individually and in combination (AC-PACs+LL-37 and EGCG+LL-37) were 
      stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS). 
      Multiplex ELISA assays were used to quantify the secretion of 54 host factors, 
      including chemokines, cytokines, growth factors, matrix metalloproteinases 
      (MMPs), and tissue inhibitors of metalloproteinases (TIMPs). RESULTS: LL-37, 
      AC-PACs, and EGCG, individually or in combination, had no effect on the 
      regulation of MMP and TIMP secretion but inhibited the secretion of several 
      cytokines. AC-PACs and LL-37 acted in synergy to reduce the secretion of 
      CXC-chemokine ligand 1 (GRO-alpha), granulocyte colony-stimulating factor (G-CSF), 
      and interleukin-6 (IL-6), and had an additive effect on reducing the secretion of 
      interleukin-8 (IL-8), interferon-gamma inducible protein 10 (IP-10), and monocyte 
      chemoattractant protein-1 (MCP-1) in response to LPS stimulation. EGCG and LL-37 
      acted in synergy to reduce the secretion of GRO-alpha, G-CSF, IL-6, IL-8, and IP-10, 
      and had an additive effect on MCP-1 secretion. CONCLUSION: The combination of 
      LL-37 and natural polyphenols from cranberry and green tea acted in synergy to 
      reduce the secretion of several cytokines by an LPS-stimulated 3D co-culture 
      model of oral mucosal cells. Such combinations show promising results as 
      potential adjunctive therapies for treating inflammatory periodontitis.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Lombardo Bedran, Telma Blanca
AU  - Lombardo Bedran TB
AD  - Department of Oral Diagnosis and Surgery, Araraquara Dental School, State 
      University of Sao Paulo, Sao Paulo, Brazil.
FAU - Palomari Spolidorio, Denise
AU  - Palomari Spolidorio D
AD  - Department of Physiology and Pathology, Araraquara Dental School, State 
      University of Sao Paulo, Sao Paulo, Brazil.
FAU - Grenier, Daniel
AU  - Grenier D
AD  - Oral Ecology Research Group, Faculty of Dentistry, Universite Laval, Quebec City, 
      QC, Canada. Electronic address: Daniel.Grenier@greb.ulaval.ca.
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150227
PL  - England
TA  - Arch Oral Biol
JT  - Archives of oral biology
JID - 0116711
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Plant Extracts)
RN  - 0 (Proanthocyanidins)
RN  - 0 (Tea)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - 0 (Cathelicidins)
SB  - IM
MH  - Aggregatibacter actinomycetemcomitans
MH  - Antimicrobial Cationic Peptides/*pharmacology
MH  - Catechin/*analogs & derivatives/pharmacology
MH  - *Coculture Techniques
MH  - Drug Synergism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Fibroblasts/*drug effects/metabolism
MH  - Gingiva/*cytology/metabolism
MH  - Humans
MH  - Inflammation Mediators/*metabolism
MH  - Lipopolysaccharides
MH  - Plant Extracts/*pharmacology
MH  - Proanthocyanidins/*pharmacology
MH  - *Tea
MH  - *Vaccinium macrocarpon
MH  - Cathelicidins
OTO - NOTNLM
OT  - Cathelicidin
OT  - Cranberry
OT  - Epithelial cell
OT  - Fibroblast
OT  - Green tea
OT  - Periodontal disease
EDAT- 2015/03/21 06:00
MHDA- 2016/02/13 06:00
CRDT- 2015/03/21 06:00
PHST- 2014/11/14 00:00 [received]
PHST- 2015/01/22 00:00 [revised]
PHST- 2015/02/21 00:00 [accepted]
PHST- 2015/03/21 06:00 [entrez]
PHST- 2015/03/21 06:00 [pubmed]
PHST- 2016/02/13 06:00 [medline]
AID - S0003-9969(15)00049-7 [pii]
AID - 10.1016/j.archoralbio.2015.02.021 [doi]
PST - ppublish
SO  - Arch Oral Biol. 2015 Jun;60(6):845-53. doi: 10.1016/j.archoralbio.2015.02.021. 
      Epub 2015 Feb 27.