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Abstract: Interleukin-27 (IL-27) is an IL-12-related cytokine that can promote both anti- and pro-inflammatory immune responses. In this study, we used the promonocytic cell line THP-1, an established model for monocytes to investigate if the immunoregulatory role of IL-27 is in part due to effects on major histocompatibility complex (MHC) Ag presentation. We find that IL-27 induces mRNA and surface expression of class II MHC in THP-1 cells. IL-27 also increases class I MHC heavy chain, β2m, and TAP-1 transcripts, leading to an increased surface expression of class I MHC. In addition, IL-27 enhances expression of costimulatory molecules CD80 and CD86 and adhesion molecule CD54. Expression of the class II transactivator (CIITA) isoforms III and IV, but not I, transcripts increases in response to IL-27. Our data suggest that the pro-inflammatory role of IL-27 is mediated in part through increased expression of key molecules involved in the class II and class I MHC pathways. [Copyright &y& Elsevier]