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Porphyromonas gingivalis ,Treponema denticola , andTannerella forsythia are periodontal pathogens associated with the etiology of adult periodontitis as polymicrobial infections. Recent studies demonstrated that oral infection withP. gingivalis induces both periodontal disease and atherosclerosis in hyperlipidemic and proatherogenic ApoE−/− mice. In this study, we explored the expression of microRNAs (miRNAs) in maxillas (periodontium) and spleens isolated from ApoE−/− mice infected withP. gingivalis ,T. denticola , andT. forsythia as a polymicrobial infection. miRNA expression levels, including miRNA miR-146a, and associated mRNA expression levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) were measured in the maxillas and spleens from mice infected with periodontal pathogens and compared to those in the maxillas and spleens from sham-infected controls. Furthermore, in response to these periodontal pathogens (as mono- and polymicrobial heat-killed and live bacteria), human THP-1 monocytes demonstrated similar miRNA expression patterns, including that of miR-146a,in vitro . Strikingly, miR-146a had a negative correlation with TNF-α secretionin vitro , reducing levels of the adaptor kinases IL-1 receptor-associated kinase 1 (IRAK-1) and TNF receptor-associated factor 6 (TRAF6). Thus, our studies revealed a persistent association of miR-146a expression with these periodontal pathogens, suggesting that miR-146a may directly or indirectly modulate or alter the chronic periodontal pathology induced by these microorganisms.

infection and immunity

Polymicrobial Infection with Periodontal Pathogens Specifically Enhances MicroRNA miR-146a in ApoE <sup>−/−</sup> Mice during Experimental Periodontal Disease

Polymicrobial Infection with Periodontal Pathogens Specifically Enhances MicroRNA miR-146a in ApoE −/− Mice during Experimental Periodontal Disease

Polymicrobial Infection with Periodontal Pathogens Specifically Enhances MicroRNA miR-146a in ApoE ^−/− Mice during Experimental Periodontal Disease