Triclosan inhibition of acute and chronic inflammatory gene pathways.
OBJECTIVE
We sought to determine whether triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether), an extensively used anti-plaque agent with broad-spectrum anti-microbial activity, with reported anti-inflammatory effects via inhibition of prostaglandin E2 and interleukin 1 (IL-1)beta, could also more broadly suppress multiple inflammatory gene pathways responsible for the pathogenesis of gingivitis and periodontitis.


METHODS
As an exploratory study, the effects of triclosan on the inflammatory gene expression profile were assessed ex vivo using peripheral whole blood samples from eight periodontally healthy donors. Ten-millilitres whole blood aliquots were incubated 2 h with 0.3 microg/ml Escherichia coli lipopolysaccharide (LPS) with or without 0.5 microg/ml triclosan. Affymetrix microarray gene expression profiles from isolated leucocytes and pathway-specific quantitative polymerase chain reaction arrays were used to investigate changes in expression of target cytokines and cell signalling molecules.


RESULTS
Ex vivo human whole blood assays indicated that triclosan significantly down-regulated the LPS-stimulated expression of Toll-like receptor signalling molecules and other multiple inflammatory molecules including IL-1 and IL-6 and the dampening of signals that activate the T-helper type 1 acquired immune response via suppression of CD70 with concomitant up-regulation of growth factors related to bone morphogenetic protein (BMP)2 and BMP6 synthesis.


CONCLUSIONS
Anti-inflammatory effects were found in this exploratory survey, including suppression of microbial-pathogen recognition pathway molecules and the suppression of acute and chronic mediators of inflammation.
Barros
Silvana P
SP
School of Dentistry, Center for Oral and Systemic Diseases, North Carolina Oral Health Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27709, USA. silvana_barros@dentistry.unc.edu
Wirojchanasak
Sodsi
S
Barrow
David A
DA
Panagakos
Fotinos S
FS
Devizio
William
W
Offenbacher
Steven
S
D000208:Acute Disease; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000235:genetics; D055418:Bone Morphogenetic Protein 6 / Q000096:biosynthesis / Q000235:genetics; D053282:CD27 Ligand / Q000037:antagonists & inhibitors; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D014260:Triclosan / Q000494:pharmacology*; D055815:Young Adult; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D055396:Bone Morphogenetic Protein 2; D055418:Bone Morphogenetic Protein 6; D053282:CD27 Ligand; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014260:Triclosan; D000093242:Interleukin-6 Inhibitors