The endogenous interferon system in anal squamous epithelial lesions with different grades from HIV-positive individuals

Anal intraepithelial lesions (ASILs) are considered as precursors of anal c ancer. The incidence of high-grade ASIL (HSIL) and progression of low-grade ASIL (LSIL) to HSIL are high in HIV-positive men. Endogenous cytokines, su ch as interferons (IFNs) play an important role in the regulation of prolif eration and immune responses in epithelial cells, and thus, they might cont rol the above-mentioned progression events. Accordingly, we determined mRNA levels of IFN-gamma and IFN-gamma receptors, levels of IFN-gamma receptor- associated kinases (JAK1 and TYK2) and signalling molecules (signal transdu cer and activator of transcription-1 [STAT1], STAT3, interferon-responsive- factor-l [IRF-1] and IRF-2) as well as inhibitors of cytokine signalling (p rotein inhibitor of activated STAT1 [PIAS1] and suppressor of cytokine sign alling 2 [SOCS2]) in biopsies of anal condylomas, LSILs as well as HSILs fr om HIV-positive individuals by a semi-quantitative reverse transcribed-poly merase chain reaction (RT-PCR) method. We found that HSIL significantly dif fers in expression of these genes from LSIL and condylomas. Expression prof ile of HSIL samples showed activation of STAT3 signalling, probably account ing for the observed high levels of genes that support cellular proliferati on (IRF-2, c-fos and c-myc). Decreases in levels of suppressors (IFN-gamma, and IRE-1) and JAK1 kinase, but increases in levels of inhibitors of cytok ine signalling (PIAS1 and SOCS2) might also contribute to the altered cytok ine signalling in HSIL biopsies. These findings might reveal important mole cular events associated with progression of LSIL to HSIL in HIV-infected me n.