title: Porphyromonas gingivalis lipopolysaccharide induces miR-146a without altering the production of inflammatory cytokines.
abstract: Lipopolysaccharide (LPS) from Porphyromonas gingivalis, an oral Gram-negative bacterium, acts as a virulence factor for periodontal disease. Although P. gingivalis LPS does not induce proinflammatory cytokines as strongly as Escherichia coli LPS, it is still able to exploit negative Toll-like receptor (TLR) regulatory pathways and facilitate pathogen persistence. Recent reports suggest that microRNAs (miRNAs) are also involved in the regulation of TLR signaling. Here, we demonstrate that P. gingivalis LPS strongly induces miRNA-146a expression in THP-1 cells and THP-1-derived macrophages. However, the inhibition or overexpression of miR-146a, through the transfection of a specific inhibitor or precursor, respectively, had little effect on cytokine production in macrophages stimulated with P. gingivalis LPS. Moreover, the expression of interleukin-1 associated-kinase-1 (IRAK-1) and tumor-necrosis factor (TNF) receptor-associated factor-6 (TRAF6), potential target molecules of miR-146a, were not affected by the stimulation with P. gingivalis LPS. Because TLR signaling induces various negative regulators, these results call into question the role of miR-146a in cells stimulated with TLR ligands.
authors.affiliation: Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honda
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Sayuri
authors.initials: S
authors.lastname: Miyauchi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D035683:MicroRNAs / Q000096:biosynthesis*; D010518:Periodontitis / Q000276:immunology* / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D048029:TNF Receptor-Associated Factor 6 / Q000096:biosynthesis / Q000235:genetics; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; D053592:Interleukin-1 Receptor-Associated Kinases