• 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.

• Parasites, Hosts and Diseases
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• 제59권6호
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• pp.557-564
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• 2021

Macrophages play a key role in chronic inflammation, and are the most abundant immune cells in the tumor microenvironment. We investigated whether an interaction between inflamed prostate cancer cells stimulated with Trichomonas vaginalis and macrophages stimulates the proliferation of the cancer cells. Conditioned medium was prepared from T. vaginalis-infected (TCM) and uninfected (CM) mouse prostate cancer (PCa) cell line (TRAMP-C2 cells). Thereafter conditioned medium was prepared from macrophages (J774A.1 cell line) after incubation with CM (MCM) or TCM (MTCM). When TRAMP-C2 cells were stimulated with T. vaginalis, protein and mRNA levels of CXCL1 and CCL2 increased, and migration of macrophages toward TCM was more extensive than towards CM. Macrophages stimulated with TCM produced higher levels of CCL2, IL-6, TNF-α, their mRNAs than macrophages stimulated with CM. MTCM stimulated the proliferation and invasiveness of TRAMP-C2 cells as well as the expression of cytokine receptors (CCR2, GP130, CXCR2). Importantly, blocking of each cytokine receptors with anti-cytokine receptor antibody significantly reduced the proliferation and invasiveness of TRAMP-C2 cells. We conclude that inflammatory mediators released by TRAMP-C2 cells in response to infection by T. vaginalis stimulate the migration and activation of macrophages and the activated macrophages stimulate the proliferation and invasiveness of the TRAMP-C2 cells via cytokine-cytokine receptor binding. Our results therefore suggested that macrophages contribute to the exacerbation of PCa due to inflammation of prostate cancer cells reacted with T. vaginalis.

• Molecules and Cells
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• 제43권11호
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• pp.964-973
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• 2020

Recent studies have highlighted that early enhancement of the glycolytic pathway is a mode of maintaining the proinflammatory status of immune cells. Thiamine, a wellknown co-activator of pyruvate dehydrogenase complex, a gatekeeping enzyme, shifts energy utilization of glucose from glycolysis to oxidative phosphorylation. Thus, we hypothesized that thiamine may modulate inflammation by alleviating metabolic shifts during immune cell activation. First, using allithiamine, which showed the most potent anti-inflammatory capacity among thiamine derivatives, we confirmed the inhibitory effects of allithiamine on the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and maturation process in dendritic cells. We applied the LPS-induced sepsis model to examine whether allithiamine has a protective role in hyper-inflammatory status. We observed that allithiamine attenuated tissue damage and organ dysfunction during endotoxemia, even when the treatment was given after the early cytokine release. We assessed the changes in glucose metabolites during LPS-induced dendritic cell activation and found that allithiamine significantly inhibited glucose-driven citrate accumulation. We then examined the clinical implication of regulating metabolites during sepsis by performing a tail bleeding assay upon allithiamine treatment, which expands its capacity to hamper the coagulation process. Finally, we confirmed that the role of allithiamine in metabolic regulation is critical in exerting anti-inflammatory action by demonstrating its inhibitory effect upon mitochondrial citrate transporter activity. In conclusion, thiamine could be used as an alternative approach for controlling the immune response in patients with sepsis.

• Journal of Periodontal and Implant Science
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• 제30권3호
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• pp.687-700
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• 2000

Antigen-specific T cell clones were obtained from mice immunized with Fusobacterium nucleatum ATCC 10953(F .nucleatum) and/or Porphyromonas gingi valis 381(P. gingivalis). 10 Balb/c mice per group were immunized with F. nucleatum followed by P. gingivalis, or with P. gingivalis alone by intraperitoneal injection of viable microorganisms. Spleen T cells were isolated and stimulated in vitro with viable P. gingivalis cells to establish P. gingivalisspecific T cell clones. T cell phenotypes and cytokine profiles were determined along with T cell responsiveness to F .nucleatum or P. gingivalis. Serum IgG antibody titers to F. nucleatum or P. gingivalis were also determined by ELISA. All the T cell clones derived from mice immunized with F. nucleatum followed by P. gingivalis demonstrated Th2 subsets, while those from mice immunized with P. gingivalis alone demonstrated Th1 subsets based on the flow cytometric analysis and cytokine profiles, All T cells clones from both groups were cross-reactive to both P. gingivalis and F. nucleatum antigens. Phenotypes of T cell clones were all positive for CD4. Mean post-immune serum IgG antibody levels to F. nucleatum or P . gingivalis were significantly higher than the pre-immune levels(p <0.01, respectively). There were no significant differences in the antibody titers between the two groups. It was concluded that P. gingivalis-specific T cells initially primed by cross-reactive F. nucleatum antigens were polarized to Th2 subsets, while T cells stimulated with P. gingivalis alone maintained the profile of Th1 subset.

• 대한한방내과학회지
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• 제30권3호
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• pp.582-593
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• 2009

Background and Objective : Allergy is defined as an altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. This study was to evaluate the effect of oriental materia medica on IL-5 secretion in the mouse spleen cell. Methods : We used the splenocytes of mouse 8 weeks after its birth, and then cultivated those into the 2 experimental groups and a control group for 48 hours. The culture media of the experimental groups were made of $1{\mu}g/ml$, $10{\mu}g/ml$ oriental materia medica, representative. And the culture media of control group was given no oriental materia medica. Then, we assayed the quantity of cytokine-expression by the sandwich ELISA. The quantities of cytokine-expression of the experimental groups were compared with that of the control group, which was standardized. These methods were used for all of the oriental materia medica treated. Results : Some oriental materia medica inhibit the secretion of IL-5 in both $1{\mu}g/ml$ and $10{\mu}g/ml$ culture media. These were Acori Rhizoma, Luffae Fasciculus Vascularis, Amomi Rotundi Fructus, Schisandrae Fructus, Biotae Semen, Clematis armandii, Dioscoreae Sativa Rhizoma, Coicis Semen, Sophorae Flos, Oroxyli Semen, Aurantii Semen, Pini Nodi Lignum. Conclusion : This study indicates that some oriental materia medica inhibit the secretion of IL-5 and are beneficial for allergic disease.

• Journal of Microbiology and Biotechnology
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• 제26권3호
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• pp.469-476
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• 2016

This study was undertaken to evaluate the immunomodulatory effect of dead nano-sized Lactobacillus plantarum (nLp) in RAW 264.7 cells and murine primary splenocytes. nLp is a dead, shrunken, processed form of L. plantarum nF1 isolated from kimchi (a traditional Korean fermented cabbage) and is less than 1 μm in size. It was found that nLp treatment stimulated nitric oxide (NO) production more in RAW 264.7 macrophages than pure live L. plantarum (pLp), and that the stimulatory properties were probably largely derived from its cell wall. In addition, nLp induced murine splenocyte proliferation more so than pLp; in particular, a high dose of nLp (1.0 × 10¹¹ CFU/ml) stimulated proliferation as much as lipopolysaccharide at 2 μg/ml. Moreover, according to our cytokine profile results in splenocytes, nLp treatment promoted Th1 (TNF-α, IL-12 p70) responses rather than Th2 (IL-4, IL-5) responses and also increased Th17 (IL-6, IL-17A) responses. Thus, nLp stimulated NO release in RAW 264.7 cells and induced splenocyte proliferation more so than pLp and stimulated Th1 and Th17 cytokine production. These findings suggested that dead nLp has potential use as a functional food ingredient to improve the immune response, and especially as a means of inducing Th1/Th17 immune responses.

• 대한의생명과학회지
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• 제20권3호
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• pp.162-167
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• 2014

Tuberculosis (TB) is one of the major global health problems and it has been estimated that in 5~10% of Mycobacterium tuberculosis (MTB)-infected individuals, the infection progresses to an active disease. Numerous cytokines and chemokines regulate immunological responses at cellular level including stimulation and recruitment of wide range of cells in immunity and inflammation. In the present study, the mRNA expression levels of eight host immune markers containing of IFN-${\gamma}$, TNF-${\alpha}$, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11 in whole blood cells from active pulmonary TB patients were measured after T-cell mitogen (PHA) and MTB specific antigens (ESAT-6, CFP-10, and TB7.7). Among the TH1-type factors, IFN-${\gamma}$ mRNA expression was peaked at 4 h, TNF-${\alpha}$ and IL-2R mRNA expression was significantly high at the late time points (24 h) in active TB patients, TH2-type cytokine (IL4 and IL10) mRNA expression levels in both active TB and healthy controls samples did not changed significantly, and the mRNA expression of the three IFN-${\gamma}$-induced chemokines (CXCL9, CXCL10, and CXCL11) were peaked at the late time points (24 h) in active TB patients after MTB specific antigen stimulation. In conclusion, the mRNA expression patterns of the TB-related immune markers in response to the T-cell mitogen (PHA) differed from those in response to MTB specific antigens and these findings may helpful for understanding the relationship between MTB infection and host immune markers in a transcripts level.

• Parasites, Hosts and Diseases
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• 제44권3호
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• pp.209-219
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• 2006

Toxoplasma gondii has been shown to result in life-threatening encephalitis in immunocompromised patients after reactivation of dormant parasites. In order to obtain information on immune responses related to this phenomenon, BALB/c mice were infected with 25 cysts of the 76K strain of T. gondii, then, treated orally with dexamethasone (Toxo/Dexa-treated group) in order to reactivate the chronic toxoplasmosis. None of the T. gondii-infected mice died during the experimental periods, whereas the Toxo/Dexa-treated mice evidenced a significant attenuation of survival periods. Toxoplasma-specific IgG2a, IgA and IgM titers in sera were significantly depressed in the Toxo/Dexa-treated mice; however, the IgG1 sera titers were similar to those seen in the Toxoplasma-infected mice. The percentages of CD4+ and $CD8\alpha+$ T cells in the Toxo/Dexa-treated mice were significantly reduced 2 weeks after dexamethasone treatment. $IFN-\gamma$ and IL-10 production levels in the Toxo/Dexa-treated mice were depressed significantly, whereas IL-4 production was increased temporarily. The expression levels of the Toxoplasma-specific P30 and B1 genes were found to have been increased in the Toxo/Dexa-treated mice in comparison with the Toxoplasma-infected mice. Collectively, the findings of this study demonstrate that reactivation of murine toxoplasmosis as the result of dexamethasone treatment induced a depression in Th1 immune responses, whereas Th2 immune responses were not significantly influenced.

• 한국축산식품학회지
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• 제31권3호
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• pp.420-427
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• 2011

The use of lactic-acid bacteria (LAB) is effective for preventing and curing immune disorders by activating the immune system in the digestive tract and the consequent immune response in the blood. In this study, LAB and mixed LABs were used in an atopic dermatitis (AD) mouse model. Alleviation of AD was observed based on the change in cytokine level and immunohistochemical staining. An ex vivo test showed that immunoglobulin-E and interleukin (IL)-4 levels were significantly lower in all groups treated with LAB than in the group treated with only 1-chloro-2,4-dinitrobenzene. Results of an in vivo test based on the ex vivo results showed that the scratch score decreased in all groups treated with the LAB and particularly decreased in the group treated with mixed LABs. Additionally, the T helper (Th) 1 cytokines interferon-gamma and IL-12p40 were upregulated by the LAB and mixed-LABs, whereas levels of the Th2 cytokine IL-4 were downregulated in a mouse model of AD-like skin lesions. Furthermore, hematoxylin & eosin and immunohistochemical staining of the dorsal area of the mice in each group showed that AD improved in the LAB-treated groups. These results suggest that LAB and mixed LABs inhibit the development of AD in NC/Nga mice by suppressing the Th2 cell response and increasing the Th1 cell response. Our results indicate that mixed LABs are better than LAB for treating AD-like skin lesions.

• 동의생리병리학회지
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• 제24권3호
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• pp.446-451
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• 2010

We investigated whether oral administration with capsicum extract (Capsicum annuum var. cheongyang) would affect the immune system by examining the immune cells of Peyer's patch (PP), a gut associated lymphoid tissue, ex vivo. The mice were orally administrated with capsicum extract (100 mg/kg/day), capsaicin (10 mg/Kg), and the vehicle for four consecutive days, and PPs were isolated from intestines 2 days later. When the PP cells were cultured in the presence of Concanavalin A for 72 hr, the levels of cytokines, including IL-2 and IFN-${\gamma]$, were dramatically increased, while the levels of IL-4 remained unchanged compared with the control. Data from the FACS analysis of PP cells indicated that capsicum extract significantly increased the number of CD3+ and CD4+ T cells as well as CD 19+ B cells compared with the control but not CD11b+ cells. Furthermore, the percentages of IL-2+ /CD4+ cells and IFN-${\gamma}+$/CD4+ were greatly increased. These data suggested that oraladministration with capsicum extract might activate the CD4+ T cells leading to cytokine production as well as CD19+ B cells in Peyer's patches. As such, capsicum extract might have potential as an immune modulating agent.