Suppresses Microbe-Induced Production of IL-1β in Human Normal and Cancerous Oral Cells through the PI3K/Akt/GSK-3β Axis.

Poor oral hygiene (POH) is associated with oral squamous cell carcinoma (OSCC). Oral microbes often proliferate due to POH. Array data show that plays a role in immunity against pathogens. We investigated whether regulates the production of oral microbe-induced IL-1β, an oncogenic proinflammatory cytokine in OSCC. We demonstrated the presence of () in 11.3% of OSCC tissues ( = 80). and the oral bacterium stimulate higher levels of IL-1β secretion by -deficient OSCC cells than by -expressing oral cells. SC5314 increased OSCC incidence in 4-NQO (a synthetic tobacco carcinogen) and arecoline-cotreated mice. Loss and gain of function significantly increased and decreased, respectively, SC5314-induced IL-1β production in oral and OSCC cell lines. Mechanistic studies showed that deficiency increased active phosphorylated Akt upon SC5314 stimulation and subsequent inhibitory phosphorylation of GSK-3β by activated Akt. PI3K and Akt inhibitors and expression of the constitutively active mutant GSK-3β significantly reduced the SC5314-stimulated IL-1β production in -deficient cells. These results indicate that the PI3K/Akt/pGSK-3β signaling pathway contributes to -mediated inhibition of oral microbe-induced IL-1β production, suggesting that may determine the pathogenic role of oral microbes in POH-associated OSCC.