Treatment of melanoma cell lines with IFN-γ induces the switch from proteasome (PS) to immunoproteasome (iPS). This finding has profound implications for the immunobiology of melanoma cells since certain peptides (such as Melan-Amart1 27-35) are cleaved differently by iPS, thus implying a different ability to be presented by HLA class I molecules. IFN-α is a cytokine not only produced during infectious diseases, but also used in the treatment of certain cancers. Nevertheless, the effects of IFN-α on the switch of PS to WS are largely unknown. A comparison of the effect of both IFN-α and IFN-γ was thus carried out on melanoma cell lines. RT-PCR showed that mRNA for iPS subunits (i.e. LMP-2, LMP-7 and MECL-1) was detectable both in untreated and IFN-treated melanoma cells. Immunoblotting analysis revealed that while IFN-γ was able to consistently induce the switch from PS to iPS, IFN-α treatment did not, possibly due to post-transcriptional event(s) blocking the expression of iPS-specific subunits. Finally, Melan-Amart1 27-35 peptide was found only in the HPLC-MS spectra from both untreated and IFN-α-treated cells, but not upon IFN-γ treatment. Altogether, these data demonstrate that IFN-α does not induce the switch from PS to iPS.
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