Abstract
BackgroundInterleukin-32 (IL-32) is an important factor in innate and adaptive immune responses, which activates the p38MAPK, NF-kappa B and AP-1 signaling pathways. Recent reports have highlighted that IL-32 is regulated during viral infection in humans.MethodsEnzyme-linked immunosorbent assays (ELISA) were carried out to detect IL-32 levels in serum samples. Detailed kinetics of the transcription of IL-32 mRNA and expression of IL-32 protein during human cytomegalovirus (HCMV) infection were determined by semi-quantitative RT-PCR and western blot, respectively. The expression levels of hcmv-miR-UL112-1 were detected using TaqMan® miRNA assays during a time course of 96 hours. The effects of hcmv-miR-UL112-1 on IL-32 expression were demonstrated by luciferase assay and western blot, respectively.ResultsSerum levels of IL-32 in HCMV-IgM positive patients (indicating an active HCMV infection) were significantly higher than those in HCMV-IgM negative controls. HCMV infection activated cellular IL-32 transcription mainly in the immediately early (IE) phase and elevated IL-32 protein levels between 6 and 72 hours post infection (hpi) in the human embryonic lung fibroblast cell line, MRC-5. The expression of hcmv-miR-UL112-1 was detected at 24 hpi and increased gradually as the HCMV-infection process was prolonged. In addition, it was demonstrated that hcmv-miR-UL112-1 targets a sequence in the IL-32 3′-UTR. The protein level of IL-32 in HEK293 cells could be functionally down-regulated by transfected hcmv-miR-UL112-1.ConclusionsIL-32 expression was induced by active HCMV infection and could be functionally down-regulated by ectopically expressed hcmv-miR-UL112-1. Our data may indicate a new strategy of immune evasion by HCMV through post-transcriptional regulation.
Highlights
Interleukin-32 (IL-32) is an important factor in innate and adaptive immune responses, which activates the p38MAPK, NF-kappa B and AP-1 signaling pathways
High IL-32 levels among individuals with active Human cytomegalovirus (HCMV) infection IL-32 protein levels were measured in the sera of 40 patients with active HCMV infections (HCMV IgM positive) and 32 HCMV IgM negative control individuals by enzyme-linked immunosorbent assays (ELISA)
These results demonstrate that IL-32 may be a newly described reactive protein corresponding to active HCMV infection
Summary
Interleukin-32 (IL-32) is an important factor in innate and adaptive immune responses, which activates the p38MAPK, NF-kappa B and AP-1 signaling pathways. IL32 is associated with the induction of inflammatory responses by activating the p38MAPK, NF-kappa B and AP-1 signaling pathways. It has been implicated in inflammatory disorders, mycobacterium tuberculosis infections and inflammatory bowel disease, as well as in some autoimmune diseases, such as rheumatoid arthritis, Human cytomegalovirus (HCMV) is an ubiquitous βherpesvirus that infects a broad range of cell types in human hosts, contributing to its complex and varied pathogenesis. HCMV Infection leads to life-long persistence in 50%–90% of the population, which is generally subclinical in healthy individuals [22]. It can lead to serious complications in immunocompromised patients, such as transplant recipients or AIDS patients [23,24]
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