• BMB Reports
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• 제52권3호
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• pp.165-174
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• 2019

Interleukin-32 (IL-32) was originally identified in natural killer (NK) cells activated by IL-2 in 1992. Thus, it was named NK cell transcript 4 (NK4) because of its unknown function at that time. The function of IL-32 has been elucidated over the last decade. IL-32 is primarily considered to be a booster of inflammatory reactions because it is induced by pro-inflammatory cytokines and stimulates the production of those cytokines and vice versa. Therefore, many studies have been devoted to studying the roles of IL-32 in inflammation-associated cancers, including gastric, colon cancer, and hepatocellular carcinoma. At the same time, roles of IL-32 have also been discovered in other cancers. Collectively, IL-32 fosters the tumor progression by nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$)-mediated cytokines and metalloproteinase production, as well as stimulation of differentiation into immunosuppressive cell types in some cancer types. However, it is also able to induce tumor cell apoptosis and enhance NK and cytotoxic T cell sensitivity in other cancer types. In this review, we will address the function of each IL-32 isoform in different cancer types studied to date, and suggest further strategies to comprehensively elucidate the roles of IL-32 in a context-dependent manner.

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3561-3566
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• 2010

Interleukin 32 (IL-32) is a recently identified cytokine that induces major proinflammatory cytokines such as $TNF{\alpha}$ and IL-$1{\beta}$, which play an important role in chronic inflammatory diseases. To antagonize the biological function of IL-32 in cells, we generated RNA aptamers that could bind specifically to IL-32 protein. The highest affinity aptamer, AC3-3, successfully antagonized IL-32 by abolishing the induction of $TNF{\alpha}$ in the human lung carcinoma cells expressing IL-32. This aptamer could be used as a potent and selective antagonist against IL-32 to further elucidate the roles of IL-32 in chronic inflammatory diseases, as well as a therapeutic agent.

• IMMUNE NETWORK
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• 제14권3호
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• pp.123-127
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• 2014

Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as tumor necrosis factor-${\alpha}(TNF{\alpha})$ and IL-6 and its expression is elevated in various inflammatory autoimmune diseases, certain cancers, as well as viral infections. IL-32 gene was first cloned from activated T cells, however IL-32 expression was also found in other immune cells and non-immune cells. IL-32 gene was identified in most mammals except rodents. It is transcribed as multiple-spliced variants in the absence of a specific activity of each isoform. IL-32 has been studied mostly in clinical fields such as infection, autoimmune, cancer, vascular disease, and pulmonary diseases. It is difficult to investigate the precise role of IL-32 in vivo due to the absence of IL-32 gene in mouse. The lack of mouse IL-32 gene restricts in vivo studies and restrains further development of IL-32 research in clinical applications although IL-32 new cytokine getting a spotlight as an immune regulatory molecule processing important roles in autoimmune, infection, and cancer. In this review, we discuss the regulation and function of IL-32 in inflammatory bowel diseases and rheumatoid arthritis.

• Journal of Rheumatic Diseases
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• 제24권1호
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• pp.14-20
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• 2017

Interleukin-32 (IL-32), a recently identified pro-inflammatory cytokine, is involved in the pathogenesis and progression of infections, cancer, chronic inflammation, and autoimmune disease. IL-32γ is the most active isoform in cell death and cell activation among nine distinct isoforms of IL-32. IL-32γ potentiates both osteogenic and osteoclastogenic capacities, and is critical in the coupling of bone resorption and bone formation for maintenance of bone homeostasis. IL-32γ is strongly associated with inflammatory bone disorders such as rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. In this review, we summarize current research on the role of IL-32γ in inflammatory bone disorders, highlighting this cytokine as a novel target for prognostic marker and control of these diseases.

• IMMUNE NETWORK
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• 제14권3호
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• pp.149-155
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• 2014

We performed this study to evaluate the role of Interleukin-17 (IL-17) and Interleukin-18 (IL-18) in insulin resistance during normal pregnancy. This descriptive cross sectional study was carried out on 97 healthy pregnant women including 32, 25, and 40 individuals in the first, second, and third trimesters, respectively, and on 28 healthy non pregnant women between the autumn of 2012 and the spring of 2013. We analyzed the serum concentrations of IL-17 and IL-18 by using the enzyme linked immunosorbent assay (ELISA). Insulin resistance was measured by homeostasis model assessment of insulin resistance equation. No significant differences between the demographic data of the pregnant and non pregnant groups were observed. Insulin resistant in pregnant women was significantly higher than the controls (p=0.006). Serum IL-17 concentration was significantly different in non pregnant women and pregnant women in all gestational ages (p<0.05). Serum IL-18 level was significantly lower in subjects with first, second, and third trimesters of pregnancy in compared to non pregnant women (p<0.05). No significant correlations were found between serum IL-17 and IL-18 levels with insulin resistance (r=0.08, p=0.34 vs. r=0.01, p=0.91, respectively). Our data suggested that IL-17 and IL-18 do not appear to attribute greatly to pregnancy deduced insulin resistance during normal pregnancy.

• Journal of Microbiology and Biotechnology
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• 제24권8호
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• pp.1133-1142
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• 2014

Interleukin-32 (IL-32) is a cytokine and inducer of various proinflammatory cytokines such as $TNF{\alpha}$, IL-$1{\beta}$, and IL-6 as well as chemokines. There are five splicing variants (${\alpha}$, ${\beta}$, ${\gamma}$, ${\delta}$, and ${\varepsilon}$) and IL-$32{\gamma}$ is the most active isoform. We generated human IL-$32{\gamma}$ transgenic (IL-$32{\gamma}$ TG) mice to express high level of IL-$32{\gamma}$ in various tissues, including immune cells. The pathology of sepsis is based on the systemic inflammatory response that is characterized by upregulating inflammatory cytokines in whole body, particularly in response to gram-negative bacteria. We investigated the role of IL-$32{\gamma}$ in a mouse model of experimental sepsis by using lipopolysaccharides (LPS). We found that IL-$32{\gamma}TG$ mice resisted LPS-induced lethal endotoxemia. IL-$32{\gamma}$ reduced systemic cytokines release after LPS administration but not the local immune response. IL-$32{\gamma}TG$ increased neutrophil influx into the initial foci of the primary injected site, and prolonged local cytokines and chemokines production. These results suggest that neutrophil recruitment in IL-$32{\gamma}TG$ occurred as a result of the local induction of chemokines but not the systemic inflammatory cytokine circulation. Together, our results suggest that IL-$32{\gamma}$ enhances an innate immune response against local infection but inhibits the spread of immune responses, leading to systemic immune disorder.

• BMB Reports
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• 제41권11호
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• pp.814-819
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• 2008

Interleukin-32 (IL-32) induces a variety of proinflammatory cytokines and chemokines. The IL-32 transcript was reported originally in activated T cells; subsequently, it was demonstrated to be abundantly expressed in epithelial and endothelial cells upon stimulation with inflammatory cytokines. IL-32 is regulated robustly by other major proinflammatory cytokines, thereby suggesting that IL-32 is crucial to inflammation and immune responses. Recently, an IL-32$\alpha$-affinity column was employed in order to isolate an IL-32 binding protein, neutrophil proteinase 3 (PR3). Proteinase 3 processes a variety of inflammatory cytokines, including TNF$\alpha$, IL-$1{\beta}$, IL-8, and IL-32, thereby enhancing their biological activities. In the current study, we designed four PR3-cleaved IL-32 separate domains, identified by potential PR3 cleavage sites in the IL-32$\alpha$ and $\gamma$ polypeptides. The separate domains of the IL-32 isoforms $\alpha$ and $\gamma$ were more active than the intrinsic $\alpha$ and $\gamma$ isoforms. Interestingly, the N-terminal IL-32 isoform $\gamma$ separate domain evidenced the highest levels of biological activity among the IL-32 separate domains.

• 대한동의생리학회:학술대회논문집
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• 대한동의생리학회 2006년도 정기총회 및 동계학술대회
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• pp.32-32
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• 2006

• Asian-Australasian Journal of Animal Sciences
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• 제30권7호
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• pp.912-919
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• 2017

Objective: Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL)-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. Methods: By using fixation index ($F_{ST}$) based method, IL-32 (9375) gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and $F_{ST}$. Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8) in Codeml program of phylogenetic analysis by maximum liklihood. Results: IL-32 is detected under positive selection using the $F_{ST}$ simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%), bison (91.97%), camel (58.39%), cat (56.59%), buffalo (56.50%), human (56.13%), dog (50.97%), horse (54.04%), and rabbit (53.41%) respectively. Conclusion: This study provides evidence for IL-32 gene as under significant positive selection in goat.

• 한양메디칼리뷰
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• 제33권1호
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• pp.27-32
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• 2013

Inflammatory bowel diseases(IBD), including Crohn's disease and ulcerative colitis, are chronic inflammatory states of the intestinal tract. While the exact mechanisms inducing chronic inflammation are still unclear, it is hypothesized that the inflammation is caused in part by an inappropriate immune response to the intestinal microflora. Although inflammatory diseases are not directly linked to patient survival, symptoms of these diseases significantly decrease quality of life. The incidence rate is higher in western people than eastern people, but the incidence rate of IBD in eastern people, including Korean, is increasing. Recently, it has been reported that IL-17 is an important factor that appears to be involved in IBD induction and progression. This report reviews many recent papers reporting the relationship between IBD and IL-17, which may provide an understanding leading to new means of prevention and treatment for IBD.