Viral IL‐10 promotes cell proliferation and cell cycle progression via JAK2/STAT3 signaling pathway in nasopharyngeal carcinoma cells

Abstract

Epstein–Barr virus (EBV) is positively related to the morbidity of nasopharyngeal carcinoma (NPC) in Asia. After infection, EBV can produce several proteins, including viral interleukin‐10 (vIL‐10). But the mechanism by which vIL‐10 contributes to NPC cell proliferation and cell cycle progression is not well understood. In this study, EBV negative and positive cell lines, and the JAK2/STAT3 signal pathway inhibitor AG490 were used to illustrate the role of vIL‐10 in NPC. Cell proliferation and cell cycle were measured by CCK‐8 and flow cytometry. The expression levels of related protein were measured by Western blotting. High concentrations of vIL‐10 and IL‐6 were found in the EBV positive patients. The expression level of IL‐6 was positively related to the presence of concentration of vIL‐10. vIL‐10 can promote cancer cell proliferation and G1 to S phase transmission via upregulating the IL‐6 protein level by activating the JAK2/STAT3 signal pathway. Furthermore, EBV can induce the formation of cytotoxic T cells, whereas vIL‐10 can block the function of cytotoxic T cells. Taken together, these results suggest that vIL‐10 promotes cell proliferation and cell cycle progression via JAK2/STAT3 signaling pathway in NPC.

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

“…[197][198][199] Studies of both solid and hematological EBV-associated malignancies demonstrated higher levels of IL-10 expression compared to EBV-negative malignancies in the same anatomical region or the same cells of origin [200][201][202][203][204], which are linked to local immune suppression or local enhanced immune cell tolerance [205]. In fact, IL-10 is known to (i) downregulate the expression of major histocompatibility complex (MHC) class I and II antigens of antigen-presenting cells (APCs) [191], (ii) induce Tregs [190], which in turn (iii) inhibit T-cell proliferation and IFN-γ secretion [192], and (iv) functionally block cytotoxicity of CD8 + T cells [188] causing an immune-suppressive TME. Furthermore, in vitro knockdown of IL-10 switches latent EBV-infected tumor cells to the lytic form leading to tumor cell death.…”

“…This also synergizes with chemotherapy and thus leads to cell death [206] suggesting that IL-10 exhibits a key role in EBV-positive malignancies. Furthermore, IL-4, IL-6 and IL-13 are frequently upregulated in EBV-positive malignancies and might have relevance in the development and/or maintenance of EBV-associated malignancies [188,207,208]. Regarding IL-1β, increased levels were found in the TILs of EBV-positive GC [185].…”

Renoprotective Effect of the Recombinant Anti-IL-6R Fusion Proteins by Inhibiting JAK2/STAT3 Signaling Pathway in Diabetic Nephropathy

“…Therefore, we choose the mesangial cells treated with high glucose as an in vitro model, which was consistent with other findings. In this study, high glucose promotes the release of IL-6 which can promote cycle-related genes expression, and thus enhance the cell proliferation ( Ren et al, 2020 ). After intervention with VHH-0031, it could inhibit high-glucose-induced proliferation of mesangial cells.…”

“…Studies had indicated that high glucose could promote JAK2 and STAT3 expression ( Nahman et al, 1992 ). Cyclin D1 was one of the important target genes of STAT3 ( Ren et al, 2020 ). Cell cycle disorders is an important cause of abnormal cell proliferation.…”

Sjögren’s syndrome: a systemic autoimmune disease

“…Interestingly, EBV can produce several proteins, including viral interleukin-10 (IL-10). IL-10 in turn can trigger the production of IL-6, interfere with the cellmediated immune response and contribute to immortalization of B cells [64][65][66]. All these phenomena may play a potential role in SS immunopathogenesis including the development of SS-related lymphoma.…”