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 cancer. The incidence of high-grade ASIL (HSIL) and progression of low-grade ASIL (LSIL) to HSIL are high in HIV-positive men. Endogenous cytokines, such as interferons (IFNs) play an important role in the regulation of proliferation and immune responses in epithelial cells, and thus, they might control 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 transducer and activator of transcription-1 [STAT1], STAT3, interferon-responsive-factor-1 [IRF-1] and IRF-2) as well as inhibitors of cytokine signalling (protein inhibitor of activated STAT1 [PIAS1] and suppressor of cytokine signalling 2 [SOCS2]) in biopsies of anal condylomas, LSILs as well as HSILs from HIV-positive individuals by a semi-quantitative reverse transcribed polymerase chain reaction (RT-PCR) method. We found that HSIL significantly differs in expression of these genes from LSIL and condylomas. Expression profile of HSIL samples showed activation of STAT3 signalling, probably accounting for the observed high levels of genes that support cellular proliferation (IRF-2, c-fos and c-myc). Decreases in levels of suppressors (IFN-gamma and IRF-1) and JAK1 kinase, but increases in levels of inhibitors of cytokine signalling (PIAS1 and SOCS2) might also contribute to the altered cytokine signalling in HSIL biopsies. These findings might reveal important molecular events associated with progression of LSIL to HSIL in HIV-infected men.
Arany
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Department of Microbiology, The University of Texas Medical Branch, Galveston, TX 77555-1070, USA. iarany@utmb.edu
Muldrow
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Tyring
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D001003:Anal Canal / Q000473:pathology; D001004:Anus Diseases / Q000276:immunology / Q000473:pathology; D001005:Anus Neoplasms / Q000276:immunology* / Q000473:pathology; D001706:Biopsy; D003218:Condylomata Acuminata / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D015870:Gene Expression; D006679:HIV Seropositivity / Q000150:complications*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D018307:Neoplasms, Squamous Cell / Q000276:immunology* / Q000473:pathology; D010770:Phosphotransferases / Q000032:analysis / Q000235:genetics; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D012333:RNA, Messenger; D017471:Receptors, Interferon; D007371:Interferon-gamma; D010770:Phosphotransferases