Premium
P orphyromonas gingivalis RagB is a proinflammatory signal transducer and activator of transcription 4 agonist
Author(s) -
Hutcherson J.A.,
Bagaitkar J.,
Nagano K.,
Yoshimura F.,
Wang H.,
Scott D.A.
Publication year - 2015
Publication title -
molecular oral microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 77
eISSN - 2041-1014
pISSN - 2041-1006
DOI - 10.1111/omi.12089
Subject(s) - porphyromonas gingivalis , proinflammatory cytokine , tlr2 , periodontal pathogen , tlr4 , biology , stat protein , microbiology and biotechnology , toll like receptor , inflammation , tumor necrosis factor alpha , activator (genetics) , receptor , immunology , signal transduction , innate immune system , stat3 , biochemistry , genetics , bacteria
Summary Periodontal diseases are semi‐ubiquitous and caused by chronic, plaque‐induced inflammation. The 55‐ kD a immunodominant RagB outer membrane protein of Porphyromonas gingivalis , a keystone periodontal pathogen, has been proposed to facilitate nutrient transport. However, potential interactions between RagB and the innate response have not been examined. We determined that RagB exposure led to the differential and dose‐related expression of multiple genes encoding proinflammatory mediators [interleukin‐1α ( IL ‐1α), IL ‐1β, IL ‐6, IL ‐8 and CCL 2; all P < 0.05] in primary human monocytes and to the secretion of tumor necrosis factor and IL ‐8, but not interferon‐γ or IL ‐12. RagB was shown to be a Toll‐like receptor 2 ( TLR 2) and TLR 4 agonist that activated signal transducer and activator of transcription 4 and nuclear factor‐κB signaling, as determined by a combination of blocking antibodies, pharmaceutical inhibitors and gene silencing. In keeping, a Δ ragB mutant similarly exhibited reduced inflammatory capacity, which was rescued by ragB complementation. These results suggest that RagB elicits a major pro‐inflammatory response in primary human monocytes and, therefore, could play an important role in the etiology of periodontitis and systemic sequelae.