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Interleukin-1β enhances the production of soluble MICA in human hepatocellular carcinoma

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Abstract

The production of soluble major histocompatibility complex class I–related chain A (MICA) is thought to antagonize NKG2D-mediated immunosurveillance. Interleukin-1β (IL-1β) is elevated in patients with chronic hepatitis C (CH), and this might contribute to the escape of hepatocellular carcinoma (HCC) cells from innate immunity. In this study, we investigated the immunoregulatory role of IL-1β in the production of soluble MICA of HCC cells. First, we investigated the correlation between the serum IL-1β levels and soluble MICA in CH patients. Serum IL-1β levels were associated with soluble MICA levels in CH patients. The serum IL-1β levels of CH patients with the HCC occurrence were significantly higher than those of CH patients without HCC. We next examined the MICA production of IL-1β-treated HCC cells. Addition of IL-1β resulted in significant increase in the production of soluble MICA in HepG2 and PLC/PRF/5 cells, human HCC cells. But soluble MICA was not detected in both non-treated and IL-1β-treated normal hepatocytes. Addition of IL-1β did not increase the expressions of membrane-bound MICA on HCC cells. These were observed similarly in various cancer cells including a gastric cancer (MKN1), two colon cancers (HCT116 and HT29) and a cervical cancer (HeLa). Addition of IL-1β also increased the expression of a disintegrin and metalloproteinase (ADAM)9 in HCC cells, and the knockdown of ADAM9 in IL-1β-treated HCC cells resulted in the decrease in the production of soluble MICA of HCC cells. These findings indicate that IL-1β might enhance the production of soluble MICA by activating ADAM9 in human HCC.

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Abbreviations

IL:

Interleukin

HCC:

Hepatocellular carcinoma

MICA:

Major histocompatibility complex class I–related chain A

ADAM9:

A disintegrin and metalloproteinase 9

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Acknowledgments

This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a Grant-in-Aid for Research on Hepatitis and BSE from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Keisuke Kohga, Tomohide Tatsumi, Hinako Tsunematsu, Satoshi Aono, Satoshi Shimizu, Takahiro Kodama, Hayato Hikita, Masashi Yamamoto, Tsugiko Oze, Hiroshi Aketa, Atsushi Hosui, Takuya Miyagi, Hisashi Ishida, Naoki Hiramatsu, Tatsuya Kanto, Norio Hayashi & Tetsuo Takehara

  2. Kansai-Rosai Hospital, Amagasaki, Hyogo, 660-8511, Japan

    Norio Hayashi

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  1. Keisuke Kohga
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Correspondence to Tomohide Tatsumi.

Additional information

Keisuke Kohga and Tomohide Tatsumi have equally contributed to this work and share the first authorship.

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Kohga, K., Tatsumi, T., Tsunematsu, H. et al. Interleukin-1β enhances the production of soluble MICA in human hepatocellular carcinoma. Cancer Immunol Immunother 61, 1425–1432 (2012). https://doi.org/10.1007/s00262-012-1208-6

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  • DOI: https://doi.org/10.1007/s00262-012-1208-6

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