Type I interferon (IFN) receptor consists of two chains (Hu-IFN-alphaR1 and Hu-IFN-alphaR2), and Hu-IFN-alphaR2 takes a soluble, short, or long form (Hu-IFN-alphaR2a, Hu-IFN-alphaR2b, or Hu-IFN-alphaR2c, respectively). We examined Hu-IFN-alphaR2 expression in hepatocellular carcinoma (HCC) tissues and their corresponding non-cancerous (non-HCC) tissues. Immunohistochemically, Hu-IFN-alphaR2 expression was positive in 53 (77%) of 69 HCC tissues and in 61 (88%) of 69 non-HCC tissues. Hu-IFN-alphaR2 protein in tissue homogenates of HCC and non-HCC tissues obtained from 29 patients was measured by using ELISA kits, and the amount was 12.7+/-10.9 pg/mg protein in HCC tissue and 10.5+/-5.0 pg/mg protein in non-HCC tissue. Number of specimens in which Hu-IFN-alphaR2 level was 3 pg/mg protein or lower, or 20 pg/mg protein or higher, was one each for non-HCC, while it was 7 (24%) and 6 (21%) for HCC. RT-PCR analysis was done in 7 of the 29 HCC cases. It revealed both Hu-IFN-alphaR2a and Hu-IFN-alphaR2c were expressed in all HCC tissues and in 6 of the 7 non-HCC tissues, and Hu-IFN-alphaR2b was expressed in all HCC tissues and in 4 of the 7 non-HCC tissues. Because immunostaining intensity of Hu-IFN-alphaR2 tended to be higher in the areas with active inflammation, effects of inflammatory cytokines (IL-1alpha, IL-1beta, and TNF-alpha) on Hu-IFN-alphaR2 expression were examined on 11 HCC cell lines. As a result, TNF-alpha up-regulated Hu-IFN-alphaR2 expression in 7 of the 11 cell lines. In 3 of the 7 cell lines, up-regulation of Hu-IFN-alphaR2 on cell surface, as well as of the soluble form of Hu-IFN-alphaR2, was induced not only by TNF-alpha, but also by IL-1alpha or IL-1beta. In conclusion, both HCC and non-HCC tissues frequently express Hu-IFN-alphaR2c that is necessary for Type I IFN response. Hu-IFN-alphaR2 expression in HCC tissues is often attenuated or enhanced, and may be regulated by inflammatory cytokines.

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