TY - JOUR
T1 - Exploring the Role of IL-32 in HIV-Related Kaposi Sarcoma
AU - Semango, George
AU - Heinhuis, Bas
AU - Plantinga, Theo S
AU - Blokx, Willeke A M
AU - Kibiki, Gibson
AU - Sonda, Tolbert
AU - Mavura, Daudi
AU - Masenga, Elisante J
AU - Nyindo, Mramba
AU - van der Ven, Andre J A M
AU - Joosten, Leo A B
N1 - Publisher Copyright:
© 2018 American Society for Investigative Pathology
PY - 2018/1
Y1 - 2018/1
N2 - The intracellular proinflammatory mediator IL-32 is associated with tumor progression; however, the mechanisms remain unknown. We studied IL-32 mRNA expression as well as expression of other proinflammatory cytokines and mediators, including IL-1α, IL-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, the proangiogenic and antiapoptotic enzyme cyclooxygenase-2, the IL-8 receptor C-X-C chemokine receptor (CXCR) 1, and the intracellular kinase focal adhesion kinase-1. The interaction of IL-32 expression with expression of IL-6, TNF-α, IL-8, and cyclooxygenase-2 was also investigated. Biopsy specimens of 11 HIV-related, 7 non-HIV-related Kaposi sarcoma (KS), and 7 normal skin tissues (NSTs) of Dutch origin were analyzed. RNA was isolated from the paraffin material, and gene expression levels of IL-32 α, β, and γ isoforms, IL1a, IL1b, IL6, IL8, TNFA, PTGS2, CXCR1, and PTK2 were determined using real-time quantitative PCR. Significantly higher expression of IL-32β and IL-32γ isoforms was observed in HIV-related KS biopsy specimens compared with non-HIV-related KS and NST. 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 with non-HIV-related KS and NST. Our data suggest a possible survival mechanism by the splicing of IL-32γ to IL-32β and also IL-6, IL-8, and CXCR1 signaling pathways to reverse the proapoptotic effect of the IL-32γ isoform, leading to tumor cell survival and thus favoring tumor progression.
AB - The intracellular proinflammatory mediator IL-32 is associated with tumor progression; however, the mechanisms remain unknown. We studied IL-32 mRNA expression as well as expression of other proinflammatory cytokines and mediators, including IL-1α, IL-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, the proangiogenic and antiapoptotic enzyme cyclooxygenase-2, the IL-8 receptor C-X-C chemokine receptor (CXCR) 1, and the intracellular kinase focal adhesion kinase-1. The interaction of IL-32 expression with expression of IL-6, TNF-α, IL-8, and cyclooxygenase-2 was also investigated. Biopsy specimens of 11 HIV-related, 7 non-HIV-related Kaposi sarcoma (KS), and 7 normal skin tissues (NSTs) of Dutch origin were analyzed. RNA was isolated from the paraffin material, and gene expression levels of IL-32 α, β, and γ isoforms, IL1a, IL1b, IL6, IL8, TNFA, PTGS2, CXCR1, and PTK2 were determined using real-time quantitative PCR. Significantly higher expression of IL-32β and IL-32γ isoforms was observed in HIV-related KS biopsy specimens compared with non-HIV-related KS and NST. 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 with non-HIV-related KS and NST. Our data suggest a possible survival mechanism by the splicing of IL-32γ to IL-32β and also IL-6, IL-8, and CXCR1 signaling pathways to reverse the proapoptotic effect of the IL-32γ isoform, leading to tumor cell survival and thus favoring tumor progression.
KW - Apoptosis/genetics
KW - Chemokines, CXC/metabolism
KW - Cyclooxygenase 2/metabolism
KW - Cytokines/metabolism
KW - Disease Progression
KW - HIV Infections/complications
KW - Humans
KW - Interleukins/metabolism
KW - Sarcoma, Kaposi/metabolism
KW - Signal Transduction/physiology
KW - Skin Neoplasms/metabolism
KW - Skin/metabolism
UR - https://www.scopus.com/pages/publications/85040199999
U2 - 10.1016/j.ajpath.2017.08.033
DO - 10.1016/j.ajpath.2017.08.033
M3 - Article
C2 - 29037857
SN - 0002-9440
VL - 188
SP - 196
EP - 203
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -