AUTHOR=Kuo Hsing-Chun , Chang Li-Ching , Chen Te-Chuan , Lee Ko-Chao , Lee Kam-Fai , Chen Cheng-Nan , Yu Hong-Ren 

TITLE=Sterol Regulatory Element-Binding Protein-1c Regulates Inflammasome Activation in Gingival Fibroblasts Infected with High-Glucose-Treated Porphyromonas gingivalis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=6

YEAR=2016

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2016.00195

DOI=10.3389/fcimb.2016.00195

ISSN=2235-2988

ABSTRACT=<p><bold>Background:</bold><italic>Porphyromonas gingivalis</italic> is a major bacterial species implicated in the progression of periodontal disease, which is recognized as a common complication of diabetes. The interleukin (IL)-1β, processed by the NLR family pyrin domain containing 3 (NLRP3) inflammasome, has been identified as a target for pathogenic infection of the inflammatory response. However, the effect of <italic>P. gingivalis</italic> in a high-glucose situation in the modulation of inflammasome activation in human gingival fibroblasts (HGFs) is not well-understood.</p><p><bold>Methods:</bold><italic>P. gingivalis</italic> strain CCUG25226 was used to study the mechanisms underlying the regulation of HGF NLRP3 expression by the infection of high-glucose-treated <italic>P. gingivalis</italic> (HGPg).</p><p><bold>Results:</bold> HGF infection with HGPg increases the expression of IL-1β and NLRP3. We further demonstrated that the upregulation of sterol regulatory element-binding protein (SREBP)-1c by activation of the Akt and p70S6K pathways is critical for HGPg-induced NLRP3 expression. We showed that the inhibition of Janus kinase 2 (JAK2) blocks the Akt- and p70S6K-mediated SREBP-1c, NLRP3, and IL-1β expression. The effect of HGPg on HGF signaling and NLRP3 expression is mediated by β1 integrin. In addition, gingival tissues from diabetic patients with periodontal disease exhibited higher NLRP3 and SREBP-1c expression.</p><p><bold>Conclusions:</bold> Our findings identify the molecular pathways underlying HGPg-dependent NLRP3 inflammasome expression in HGFs, providing insight into the effect of <italic>P. gingivalis</italic> invasion in HGFs.</p>