期刊
INFLAMMATION
卷 41, 期 2, 页码 667-676出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-017-0721-3
关键词
Esophageal carcinoma; IL-18; IFN-gamma; CD8(+) T cell; Apoptosis
To investigate the potential role of interleukin-18 (IL-18) in immunomodulation during tumorigenesis of esophageal carcinoma and elucidate the underlying molecular mechanism, we employed IL-18 knockout mice for this purpose. Carcinogen 4-nitroquinoline 1-oxide (4NQO) was administrated in drinking water to induce occurrence of esophageal squamous cell carcinoma (ESCC). T cell activation as indicated by the surface CD molecules was analyzed with flow cytometry. The serous content of interferon-gamma (IFN-gamma) along with other cytokines was determined by inflammatory human cytokine cytometric bead array. The cytotoxicity assay was performed by co-culture of tumor cells with immune cells and relative cell viability was determined by lactate dehydrogenase (LDH) assay. Apoptotic cells were stained with Annexin-V/propidium iodide (PI) and analyzed by flow cytometry. Cell proliferation was measured with Cell Counting Kit-8 (CCK-8) assay. Our data demonstrated that deficiency of IL-18 promoted the progression and development of 4NQO-induced ESCC. Loss of IL-18 suppressed the activation of T cells in the esophagus. Deficiency of IL-18 inhibited the IFN-gamma production by CD8(+) T cells and natural killer (NK) cells. Absence of IL-18 inhibited the cytotoxicity of CD8(+) T cells and NK cell in vitro. Moreover, deficiency of IL-18 promoted the apoptosis of CD8(+) T cells and inhibited the proliferation of CD8(+) T cells in vitro. Our data elucidated the immunomodulatory role of IL-18 during tumorigenesis of ESCC, whose deficiency compromised antitumor immunity and contributed to immune escape of esophageal carcinoma. Our results also indicated the therapeutic potential of exogenous IL-18 against ESCC, which warrants further investigations.
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