Expression of interleukin-23 and its receptors in human squamous cell carcinoma of the oral cavity

Abstract

Interleukin (IL)-23 is a heterodimeric cytokine comprising IL-12p40 and the recently cloned IL-23-specific p19 subunit. Like IL-12, IL-23 is expressed predominantly by activated dendritic cells and phagocytic cells. Both cytokines induce interferon-gamma secretion by T cells, and antagonistically regulate local inflammatory responses in the tumor microenvironment as well as the infiltration of intra-epithelial lymphocytes. Although the expression of IL-23 in various organs has been reported, it is unclear whether IL-23 is expressed in oral cancer. The expression of IL-23 and its receptors was examined in human oral squamous cell carcinoma (HOSCC) cell lines and tissue. IL-23 and its receptor mRNAs and proteins were spontaneously expressed, and IL-23 was increased by TNF-alpha stimulation in the oral cancer cells. A cell proliferation assay confirmed that IL-23 promotes cell proliferation in oral cancer. The localization of IL-23 protein in HOSCC tissue was examined using immunohistochemistry. A positive reaction for anti-IL-23 antibody was weakly observed in the cytoplasm of inflammatory infiltrating cells and cancer cells in HOSCC tissue. Meanwhile, nuclear factor-kappaB immunoreactivity was strongly positive in HOSCC tissue, which is particularly consistent with the observation of IL-23-positive cells in SCC tissue. These data suggest that IL-23 plays a significant role in the growth and proliferation of oral cancer.