IFN-alpha mediates the up-regulation of HLA class I on melanoma cells without switching proteasome to immunoproteasome.

Abstract:

:Treatment of melanoma cell lines with IFN-gamma 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-A(mart1)(27-35)) are cleaved differently by iPS, thus implying a different ability to be presented by HLA class I molecules. IFN-alpha is a cytokine not only produced during infectious diseases, but also used in the treatment of certain cancers. Nevertheless, the effects of IFN-alpha on the switch of PS to iPS are largely unknown. A comparison of the effect of both IFN-alpha and IFN-gamma 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-gamma was able to consistently induce the switch from PS to iPS, IFN-alpha treatment did not, possibly due to post-transcriptional event(s) blocking the expression of iPS-specific subunits. Finally, Melan-A(mart1)(27-35) peptide was found only in the HPLC-MS spectra from both untreated and IFN-alpha-treated cells, but not upon IFN-gamma treatment. Altogether, these data demonstrate that IFN-alpha does not induce the switch from PS to iPS.

journal_name

Int Immunol

journal_title

International immunology

authors

Cangemi G,Morandi B,D'Agostino A,Peri C,Conte R,Damonte G,Ferlazzo G,Biassoni R,Melioli G

doi

10.1093/intimm/dxg140

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

1415-21

issue

12

eissn

0953-8178

issn

1460-2377

journal_volume

15

pub_type

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