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Objectives: ACE2, known as a host receptor involved with SARS‐CoV‐2 infection, binds to viral spike proteins for host cell entry. However, details regarding its induction and function in oral mucosal cells remain unknown. Materials and Methods: We examined ACE2 expression and its induction by transfected mimic nucleotides and pro‐inflammatory cytokines in oral keratinocytes (RT7) and fibroblasts (GT1). Subsequently, the effects of viral spike S1 protein via ACE2 on CXCL10 expression induced by pro‐inflammatory cytokines in both cells were examined. Results: ACE2 was constitutively expressed in RT7 and GT1. Transfected Poly(I:C) and Poly(dA:dT) increased ACE2 expression in those cells, while knockdown of RIG‐I decreased ACE2 expression induced by those transfected ds nucleotides. IFN‐γ and TNF‐α enhanced transfected ds nucleotides‐induced ACE2 expression in RT7 but not GT1. S1 protein alone did not affect CXCL10 expression in either cell type, whereas it enhanced IFN‐β‐induced CXCL10 in both, while immune responses of IFN‐γ‐ and TNF‐α‐induced CXCL10 enhanced by S1 protein were different between RT7 and GT1. Finally, knockdown of ACE2 decreased cytokines and S1 protein mediated‐CXCL10 levels in both cells. Conclusions: ACE2 in oral mucosal cells may contribute to development of infection and inflammation in cooperation with pro‐inflammatory cytokines following SARS‐CoV‐2 invasion. [ABSTRACT FROM AUTHOR]

Objective: Sunitinib, a targeted cancer drug, inhibits tyrosine kinases receptors and is widely used as first‐line treatment for metastatic renal cell carcinoma. Patients undergoing chemotherapy with sunitinib frequently have oral mucosal complications, such as oral stomatitis, though cytotoxic effects of the drug on oral keratinocytes remain unknown. Methods: The effects of sunitinib on immortalized oral keratinocytes, RT7 cells, in regard to cell injury and apoptosis, as well as apoptosis‐mediated signaling pathways were investigated. Results: Sunitinib treatment caused a significant increase in lactate dehydrogenase (LDH) in RT7 cells and primary oral keratinocytes. Additionally, the drug induced apoptosis‐related events, such as DNA fragmentation, decreased anti‐apoptotic Bcl‐2 protein expression, and induction of cleaved PARP and caspase 3/9 in RT7 cells. Furthermore, phosphorylation of p38 MAPK, but not of ERK or JNK, was increased. On the contrary, constitutive phosphorylated STAT3 was decreased by sunitinib treatment, which was recovered by exposure to SB203580, a p38 MAPK inhibitor. Finally, SB203580 was found to reduce sunitinib‐induced cell injury and apoptosis. Conclusion: The present results indicate that sunitinib promotes cell injury and apoptosis in oral keratinocytes via p38 activation and STAT3 downregulation. Sunitinib‐mediated oral complications may be associated with cytotoxic effects of the drug on oral keratinocytes. [ABSTRACT FROM AUTHOR]

Purpose: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer. Methods: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated. Results: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15–2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03–1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01–1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63–34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23–9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients. Conclusion: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Double‐strand (ds) DNA‐enveloped viruses can cause oral infection. Our aim is to investigate whether oral mucosal cells participate in immune response against cytosolic dsDNA invasion. Methods: We examined the response to transfected herpes simplex virus (HSV) dsDNA via intracellular receptors in oral keratinocytes (RT7) and fibroblasts (GT1), and the effect of TNF‐α on those responses. Results: Transfected dsDNA increased CXCL10 expression via NF‐κB activation in both cell types, while those responses were inhibited by knockdown of RIG‐I, an RNA sensor. Although IFI16, a DNA sensor, was expressed in the nuclei of both types, its knockdown decreased transfected dsDNA‐induced CXCL10 expression in GT1 but not RT7 cells. IFI16 in GT1 cells was translocated into cytoplasm from nuclei, which was attributed to immune response to cytosolic dsDNA. TNF‐α enhanced transfected dsDNA‐induced CXCL10, and knockdown of IFI16 decreased TNF‐α and dsDNA‐driven CXCL10 expression in both RT7 and GT1 cells. Finally, the combination of TNF‐α and transfected dsDNA resulted in translocation of IFI16 from nuclei to cytoplasm in RT7 cells. Conclusion: RIG‐I and IFI16 in oral mucosal cells may play important roles in host immune response against DNA viral infection, while TNF‐α contributes to development of an antiviral system via those intracellular receptors. [ABSTRACT FROM AUTHOR]