IL-2 and IL-15 play an important roles in regulating the lymphocyte function and homeostasis. Advances in understanding of the cellular and molecular biology of IL-2 and IL-15 and their receptor complex have provided rationale to better utilize them to expand and activate immune effectors in patients with cancer. These two cytokines stimulate similar responses from lymphocytes in vitro, but play markedly distinct roles in lymphoid biology in vivo. Their distinct physiological functions can be ascribed to distinct signaling pathways initiated by distinct cytokine receptor subunits, differential expression patterns of their receptors. Recently, the discovery of a novel mechanism of IL-15 cytokine signaling, trans-presentation, has provided insights into the divergent ways of these cytokine function. Although their heterotrimeric receptors have two receptor subunits in common, these two cytokines have contrasting roles in adaptive immune responses. The unique role of interleukin 2 is in the elimination of self-reactive T cells to prevent autoimmunity. By contrast, interleukin 15 is dedicated to the prolonged maintenance of memory T-cell responses to pathogens. As discussed in this article, the biology of IL-2 and IL-15 two cytokines will affect the development of novel treatment for malignancies and autoimmune diseases.
Humans ; Immunotherapy ; Interleukin-15 ; immunology ; metabolism ; Interleukin-2 ; immunology ; metabolism

Arthritis, Juvenile ; blood ; Child ; Humans ; Interleukin-15 ; blood

OBJECTIVETo construct a eukaryotic co-expression plasmid pIRES-fimA:IL15, which can be used as an immunoreaction-enhancing DNA vaccine against Porphyromonas gingivalis FimA, and investigate its expression in mammalian cells.

METHODSThe eukaryotic co-expression plasmid pIRES-fimA:IL15 was constructed by molecular cloning methods and characterized by restricted endonuclease mapping, PCR and DNA sequencing. The plasmid was transfected into mammalian cell CHO using Lipofectamine 2000. Expression of fimA gene was detected by Western blot and the protein secretion in cultural medium was analyzed by ELISA.

RESULTSEndonuclease mapping showed that the target genes fimA and IL-15 obtained by PCR had the same molecular size as predicted. The DNA sequencing data also indicated that inserted fimA gene and IL-15 gene had correct DNA sequence and orientation. The recombined plasmid could express FimA in mammalian cell CHO transfected. FimA and IL-15 could be secreted into cultural supernatant detected by ELISA.

CONCLUSIONA new eukaryotic co-expression plasmid pIRES-fimA: IL15 was constructed and it could be applied for further immunization in animal as an effective anti-Porphyromonas gingivalis vaccine.

The study aims to explore the active molecules of traditional Chinese medicine that specifically bind to interleukin-15 receptor α (IL-15Rα) using molecular docking and surface plasmon resonance (SPR) technology. AutoDock molecular docking software was used to perform simulated docking of more than 3 000 compounds from 48 traditional Chinese medicines at IL-15Rα and screen the specific binding compounds. Then Biocore T200 biomolecular interaction analysis system of SPR was used to confirm the binding specificity of the selected target compounds. Finally, the biological effects of the target compounds on IL-15Rα were verified by cell biological experiments. The results showed that neoprzewaquinone A (Neo) possessed the highest specific binding affinity among the active molecules from traditional Chinese medicine, and the dissociation constant (K_D) value was (0.62 ± 0.20) µmol/L. The results of cell experiment showed that Neo significantly inhibited the proliferation of Mo7e cells induced by IL-15, and the IC₅₀ was 1.075 µmol/L, approximately 1/120 of the IC₅₀ of Cefazolin (IL-15 specific antagonist). These results suggest that Neo is a specific inhibitor of IL-15Rα and may be a potential active drug for the treatment of diseases related to the dysfunction of the IL-15Rα signaling.
Molecular Docking Simulation ; Interleukin-15/pharmacology* ; Surface Plasmon Resonance ; Interleukin-15 Receptor alpha Subunit/metabolism* ; Protein Binding

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.
Cytokines ; Homeostasis ; Interferons ; Interleukin-1 ; Interleukin-10 ; Interleukin-11 ; Interleukin-12 ; Interleukin-15 ; Interleukin-17 ; Interleukin-23 ; Interleukin-27 ; Interleukin-3 ; Interleukin-33 ; Interleukin-4 ; Interleukin-6 ; Interleukin-7 ; Interleukin-8 ; Macrophage Colony-Stimulating Factor ; Necrosis ; Osteoblasts ; Osteoclasts ; RANK Ligand

OBJECTIVE: To evaluate clinical significance of interleukin 15 (IL-15) in patients with Behcet's disease (BD). METHODS: Serum samples were obtained from 31 patients with BD and 29 healthy controls. BD patients were divided into active and inactive group according to the presence of clinical manifestations on the day of sampling. Serum levels of IL-15 and IL-8 were measured by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of IL-15 and IL-8 were significantly higher in BD patients than in healthy controls (117.2+/-26.2 pg/ml versus 51.8+/-15.4 pg/ml, p<0.01, 287.7+/-100.9 pg/ml versus 138.5+/-17.2 pg/ml, p<0.01, respectively). There was a significant correlation between serum levels of IL-15 and IL-8 IL-15 levels compared with those without it (161.1+/-68.8 pg/ml versus 96.4+/-3 4 . 8pg/ml, p<0.05). Serum levels of IL-15 and IL-8 tended to be higher in active group than in inactive group, but didn't reach statistical significance. CONCLUSION: Serum level of IL-15 was elevated in patients with BD, especially those with uveitis, but it did not seem to be useful as a marker of disease activity in BD.
Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-15* ; Interleukin-8 ; Interleukins* ; Uveitis

OBJECTIVETo observe the antibody responses induced by recombinant plasmid plRES-fimA:IL15 via nasal immunization to BABL/c mice and the regulation of IL-15 to sIgA.

METHODSBABL/c mice were immunized with recombinant plasmids pIRES-fimA:IL15 and pIRES-fimA via nasal or intramuscular route. Serum IgG and salivary sIgA levels after immunization were analyzed by ELISA.

RESULTSNasal immunization with plasmids pIRESfimA:IL15 or pIRES-fimA elicited significant higher level of salivary FimA-specific sIgA responses compared with intramuscular immunization. There was no significant difference of the serum IgG responses between nasal immunization mice and intramuscular immunization mice. Nasal immunization with plasmid pIRES -fimA:IL15 elicited significant higher level of salivary sIgA response than with pIRES-fimA (P<0.05).

CONCLUSIONNasal dropping may be an effective mucosal immunization route of anti-Porphyromonas gingivalis DNA vaccine to elicit specific antibody responses in serum and oral region. IL-15 has a positive regulation effect to sIgA response.

This review attempts to define the relationship between IL-15 and autoimmune disease (AID) from IL-15's tissue distribution, expression regulation and biologic function. Meanwhile, five IL-15 dysregulation-related AIDs and four IL-15/IL-15R-targeted AID therapies are described.
Animals ; Autoimmune Diseases ; metabolism ; Humans ; Interleukin-15 ; metabolism ; Lupus Erythematosus, Systemic ; metabolism ; Multiple Sclerosis ; metabolism

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.
Humans ; Nasopharyngeal Carcinoma/genetics* ; Interleukin-15 ; Dual Oxidases ; Computational Biology ; Nasopharyngeal Neoplasms/genetics*

OBJECTIVE: Vascular endothelial growth factor (VEGF) is a potent endothelium-specific cytokine and stimulates inflammation and angiogenesis. Vascular endothelial dysfunction is one of the characteristic features of Behcet's syndrome. We previously demonstrated the possible involvement of proinflammatory cytokines (TNF-alpha, IL-15, MIF) and chemokines (IL-8, MCP-1, MIP-1alpha) in the etiopathogenesis of Behcet's syndrome and its association with disease activity. In this study, we assesed VEGF levels in patients with Behcet's syndrome and its relation with disease activity. METHODS: Serum VEGF levels of 65 patients with Behcet's syndrome and 35 healthy control volunteers were measured by enzyme-linked immunosorbent assay. The level of MIF and IL-8 were also measured in 41 pateints. Among the 65 patients, 18 patients were in active state of disease which was classified according to clinical finding. RESULTS: The mean serum VEGF levels were higher in patients of Behcet's syndrome than control subjects (332.7 pg/mL vs. 234.4 pg/mL, p=0.004) and patients with active disease hadsignificantly higher level of VEGF than inactive disease (377.8 pg/mL vs. 265.0 pg/mL, p<0.05). There is no difference in the mean serum level of VEGF between Behcet's syndrome with vascular complication and without vascular complication. Serum level of VEGF showed strong positive correlation with MIF (r=0.57, p=0.001). CONCLUSION: Serum VEGF levels are elevated in patients with Behcet's syndrome, particularly in active state and have positive correlation with MIF. These results suggest that the increased VEGF levels in serum of Behcet's syndrome patients may participate, like other proinflammatory cytokines and chemokines, in the pathogenesis of Behcet's syndrome.
Behcet Syndrome* ; Chemokines ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Equidae ; Humans ; Inflammation ; Interleukin-15 ; Interleukin-8 ; Vascular Endothelial Growth Factor A* ; Volunteers