Peroxiredoxin 1 Promotes Proinflammatory Cytokine Secretion in Human Dysplastic Oral Keratinocytes and Mouse Tongue Precancerous Tissues.

Oxidative stress, a widespread phenomenon involved in many pathological conditions, may be closely related with the progression of oral leukoplakia (OLK). Under chronic inflammation, oxidative stress could stimulate the local formation of a tumor-specific microenvironment in some types of cancer, though not well defined in oral cancer even in OLK. Peroxiredoxin 1 (Prx1), a widely expressed sulfhydryl antioxidant protein, is overexpressed in various tumors and affects tumorigenesis, cell proliferation, apoptosis, invasion, and metastasis. Prx1 also acts as a potent proinflammatory factor. Nuclear factor (NF)-κB is a member of the core dimeric transcription factor family that coordinates the inflammatory response. To investigate the role of Prx1 in oxidative stress-related inflammation in OLK, a coculture model of human dysplastic oral keratinocyte (DOK) and human epidermal fibroblast (HFF) was established and stimulated with H₂O₂. Cellular reactive oxygen species (ROS) and Prx1 levels in DOK were determined via flow cytometry and western blotting, respectively. Additionally, the levels of the inflammatory factors, interleukin (IL)-6, IL-8, IL-10, and interferon (IFN)-γ, in the conditioned medium were determined via enzyme-linked immunosorbent assay (ELISA). DOK nuclear expression of NF-κB was detected via immunofluorescence assay and western blotting. Moreover, the expression levels of inflammatory factors and the nuclear expression of NF-κB were examined in 4-nitroquinoline-1-oxide (4NQO)-induced tongue precancerous tissues of mice. H₂O₂ increased Prx1 levels and nuclear expression levels of NF-κB in DOKs and mouse tongue precancerous tissues and elevated the levels of IL-6, IL-8, IL-10, and IFN-γ secreted in the culture supernatants and mouse tongue tissues. However, Prx1 knockdown in DOK and mouse tongue tissues attenuated the upregulation of inflammatory factor and nuclear NF-κB expression levels. Overall, our results suggest that oxidative stress increases Prx1 expression, which promotes inflammatory factor expression by activating NF-κB in human DOK and mouse tongue precancerous tissues.