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Exploring the Role of IL-32 in human immunodeficiency virus-related Kaposi sarcoma.

ABSTRACT

The intracellular pro-inflammatory mediator interleukin (IL)-32 is associated with tumor progression; however, the mechanisms remain unknown. We studied the IL-32 mRNA expression as well as other pro-inflammatory cytokines and mediators including IL-1α, IL-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, the pro-angiogenic and anti-apoptotic enzyme COX-2, the IL-8 receptor CXCR1, and the intracellular kinase FAK-1. The interaction of IL-32 expression with expression of IL-6, TNFα, IL-8, and COX-2 was also investigated. Biopsies of 11 human immunodeficiency (HIV)-related, seven non HIV-related Kaposi sarcoma (KS), and seven normal skin tissues of Dutch origin were analyzed. RNA was isolated from the paraffin material and gene expression levels of IL-32α, β, and γ isoforms, IL1a, IL1b, IL6, IL8, TNFA, PTGS2, CXCR1, and PTK2 were determined using quantitative real-time PCR. Significantly higher expression of IL-32β and IL-32γ isoforms was observed in HIV-related KS biopsies compared to non HIV-related KS and normal skin tissue. The splicing ratio of the IL-32 isoforms showed IL-32γ as the highest expressed isoform, followed by IL-32β in HIV-related KS cases compared to non HIV-related KS and normal skin tissue. Our data suggest a possible survival mechanism by the splicing of IL-32γ to IL-32β and also IL-6, IL-8, and CXCR1 signalling pathways to reverse the pro-apoptotic effect of IL-32γ isoform leading to tumor cell survival and thus favoring tumor progression.