• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5513-5518
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• 2013

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.39-44
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• 2006

Type I diabetes (T1D) is an organ-specific autoimmune disease caused by the T cell-mediated destruction of the insulin-producing ${\beta}$ cells in the pancreatic islets. The onset of T1D is the consequence of a progressive destruction of islet ${\beta}$ cells mediated by an imbalance between effector $CD4^+$ T helper (Th)1 and regulatory $CD4^+$ Th2 cell function. Since interferon-alpha (IFN-${\alpha}$) has been known to modulate immune function and autoimmunity, we investigated whether administration of adenoviralmediated IFN-${\alpha}$ gene would inhibit the diabetic process in NOD mice. The development of diabetes was significantly inhibited by a single injection of adenoviral-mediated IFN-${\alpha}$ gene before 8 weeks of age. Next, we examined the hypothesis that Th2-type cytokines are associated with host protection against autoimmune diabetes, whereas Th1-type cytokines are associated with pathogenesis of T1D. The expression of IFN-${\alpha}$ induced increase of serum IL-4 and IL-6 (Th2 cytokines) levels and decrease of serum IL-12 and IFN-${\gamma}$ (Th1 cytokines) levels. Therefore, overexpression of IFN-${\alpha}$ by adenoviralmediated delivery provides modulation of pathogenic progression and protection of NOD mice from T1D.

• The Journal of Korean Medicine
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• v.19 no.2
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• pp.36-49
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• 1998

HERBA SAURURI (HS) has been known to use antiinflammatory drug. To investigated the mechanism of HS-induced NO synthesis, I evaluated the ability of protein kinase C (PKC) inhibitors such as staurosporine (STSN) or polyymyxin B to block HS-induced effects. HS alone had only a small effect, whereas in combination with $rIFN-{\gamma}$, markedly increased NO synthesis in a dose dependent manner. STSN and polymyxin B decreased NO synthesis, which had been induced by $rIFN-{\gamma}$, plus HS. Furthermore, prolonged incubation of the cells with phorbol ester, which down-regulates PKC activity abolished synergistic cooperative effect of HS with $rIFN-{\gamma}$ on NO synthesis. STSN and Polymyxin B potently inhibited HS-induced $TNF-{\alpha}$ secretion by $rIFN-{\gamma}$ plus HS. However, $rIFN-{\gamma}$ plus $TNF-{\alpha}-induced$ NO synthesis was not blocked by STSN or polymyxin B. On the other hand, tyrosine kinase inhibitor, genistein, blocked the NO synthesis and $TNF-{\alpha}$ secretion by $rIFN-{\gamma}$ plus HS. In conlusion, the present results strongly suggest that the capacity of HS to increase NO synthesis from $rIFN-{\gamma}-primed$ macrophages is the result of HS-induced $TNF-{\alpha}$ secretion via the signal transduction pathway of PKC and tyrosine kinase.

• Journal of Veterinary Clinics
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• v.27 no.6
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• pp.640-646
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• 2010

Neosporosis is a widespread parasitic disease caused by Neospora caninum, an intracellular protozoan parasite. It causes economic losses due to reproductive failure. The potential relationship between pregnancy outcomes and levels of IFN${\gamma}$, hormones, and antibodies in naturally N. caninum-infected cows was examined in the blood samples collected every 2 or 4 weeks in 26 pregnant cows from 4 different farms. The mean S/P value of seropositive nonaborting animals (n = 14) reached peak levels 15 weeks prior to parturition, and declined thereafter to parturition. The S/P value 13 weeks prior to abortion in seropositive aborting cows (n=3) remained at high levels, and abortions occurred at 20 (142 days), 26 (185 days), and 28 weeks (199 days) after artificial insemination. IFN${\gamma}$ levels in the seropositive non-aborting group varied by individuals and gestational periods; IFN${\gamma}$ levels stayed at elevated levels or increased abruptly close to abortion in seropositive aborting cows. IFN${\gamma}$ level patterns in the seronegative group (n = 9) were similar to the seropositive non-aborting group, although IFN${\gamma}$ amounts were lower than the seropositive group. The mean progesterone levels in the seropositive non-aborting and seronegative groups decreased markedly 7 weeks prior to parturition. The mean progesterone levels 5 and 7 weeks prior to abortion were lower than the other groups 5 and 7 weeks prior to parturition. The mean 17${\beta}$-estradiol levels in the seropositive aborting cows increased close to abortion; the produced amounts were lower than those of seropositive non-aborting and seronegative groups close to parturition. These results suggested that lower levels of progesterone and ${\beta}$-estradiol in Neospora-infected cows may lead to increases in IFN${\gamma}$ production and in turn may result in abortion.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.294-308
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• 2002

Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

• Parasites, Hosts and Diseases
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• v.34 no.3
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• pp.185-190
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• 1996

The TH cytokine responses of spleen cells stimulated with Con A from mice infected with Polasonimw westemcni were examined. The spleen cell culture supema- tants were assayed for TH1-specific $IFN-{\gamma}$ and TH2-specific IL-4. Cytokine responses for IL-4 peaked at three days ($410{\;}{\pm}{\;}60.9{\;}pg/ml$), persisted at a high level until the second week ($343{\;}{\pm}{\;}59.0{\;}pg/ml$), and then decreased slowly four and six weeks after infection. $IFN-{\gamma}$ production by splenocytes only increased during the first week ($151{\;}{\pm}{\;}32.3{\;}pg/ml$) and declined abruptly after the second week of infection. IFN- y production by splenocytes of infected mice was not observed during the sixth week of infection. In addition, serum IL-4 and $IFN-{\gamma}$ were measured. Serum IL-4 was not detected in substantial quantity until four to six weeks after infection. The time course of serum IL-4 was not correlated with that of IL-4 production by splenocytes. Serum $IFN-{\gamma}$ was undetectable during the entire course of infection. These results suggest that TH2 cytokine responses, rather than TH1, predominate in mice infected with P. westemcni.

• Environmental Analysis Health and Toxicology
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• v.20 no.3 s.50
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• pp.243-248
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• 2005

Mancozeb (MCZ), a polymeric complex of zinr and manganese salts of ethylene bisthiocarbamate, is widely used in agriculture as fungicidel, insecticides, and herbicides. MCZ can be occupationally and environmentally exposed to human and has been reported to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine splenocytes through evaluation of splenocytes cellularity and INF-$\gamma$ synthesis. Splenocytes were examned ex vivo from mice orally treated with various doEes of MCZ for 1 day (acute exposure, 2,100, 5,000, 10,000 mg/kg) or ior 5 consecutive days per week for 4 weeks (subacute exposure,250, 1,000, 1,500 mg/kg/day) fellowed by culture for 2 days in the presence of Con A or PHA plus IL-2. Splenocytes Iron naive mice were cultured with various concentration of MCZ (50, 500, 1,000 ng/ml) in the presence of Con A or PHA plus IL-2 for 2 days in vitro. IFN-$\gamma$ production was decreased with the in vitro exposure to all concentration of MCZ. The spleen cellularity and IFN -$\gamma$ production by splenocytes from MCZ -acutely and - subacutely exposured mice were decreased in comparision with that oi control group.

• Biomedical Science Letters
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• v.19 no.2
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• pp.90-97
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• 2013

The tuberculin skin test (TST) and interferon gamma (IFN-${\gamma}$) release assay (IGRA) have been widely used for diagnosis of latent tuberculosis infection (LTBI). In order to overcome limitations of current LTBI diagnostic methods, the development of a novel molecular assay which is able to measure the IFN-${\gamma}$ messenger RNA (mRNA) expression level after stimulation with Mycobacterium tuberculosis (MTB) specific antigen was recently developed. The ability of a molecular assay to detect MTB infection was similar to commercial IGRA however, the optimal incubation time for stimulating IFN-${\gamma}$ was not yet established. Therefore, in this study the direct comparisons of MTB Ag stimulation times (4 and 24 hrs) were performed for diagnosis of MTB infection. Data showed that the coincident rate between QFT-GIT IFN-${\gamma}$ ELISA and IFN-${\gamma}$ RT-PCR (4 hrs) was 88.35% and that of QFT-GIT and IFN-${\gamma}$ RT-PCR (24 hrs) was 70.85%. Based on a receiver operating characteristic (ROC) curve, the 4 hrs-MTB specific Ag stimulation time for IFN-${\gamma}$ RT-PCR had the significant P value, 95% CI value, and AUC (P < 0.0001, 95% CI=0.82 to 1.02, and AUC=0.9214) in comparison with 24 hrs-MTB specific Ag stimulation time (P = 0.009, 95% CI=0.06 to 0.94, and AUC=0.7711). These results show that 4-hr was the most optimal MTB Ag stimulation time for performing IFN-${\gamma}$ RT-PCR. Although semi-quantitative RT-PCR had a few analytical limitations, it might be useful as an alternative molecular diagnostic method for detecting MTB infection.

• Journal of Korean Neurosurgical Society
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• v.29 no.4
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• pp.477-484
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• 2000

Objective : Despite advances in the understanding of tumor biology and the tumor immunology, there has been no effective treatment. The Intercellular adhesion molecule-1(ICAM-1) has been shown to be important in interaction involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon($IFN-{\gamma}$) and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$). ICAM-1 has been identified as one of the ligands for lymphocyte function-associated antigen-1(LFA-1). The effectiveness of various cytokines to ICAM-1 induction on cultured human glioblastoma cell lines and potential efficacy of immunotherapy were studied. Method : Human glioblastoma cell lines, U-251 MG, U-373 MG were trypsinized and suspended at $1{\times}10^5cells/ml$ and grown on 8 well chamber slide, the cells were incubated in 0.3ml medium alone or medium containing $IFN-{\gamma}$(1000U/ml) or $TNF-{\alpha}$(250U/ml) or $IFN-{\gamma}$ plus $TNF-{\alpha}$ for 6, 12, 24, 48 and 72 hours. The coverslip were then removed and stained with a 1/30 dilution of anti-ICAM-1 antibody. Result : Surface antigen expression of ICAM-1 was increased by incubating glioblastoma cell lines with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\gamma}$ and $TNF-{\alpha}$ has induced more ICAM-1 expression on glioblastoma cell lines. Upregulation of ICAM-1 expression in an established glioblastoma cell line was of greater magnitude and more rapid following incubation with $IFN-{\gamma}$ plus $TNF-{\alpha}$. Surface antigen expression of ICAM-1 was increased for up to 48 hours after cytokine treatment on both cell lines(p<0.05). There was no difference on both cell lines(p>0.05). Conclusion : The results of the present study indicate that ICAM-1 expression in glioblastoma cell lines, U-251 MG and U-373 MG, are induced and enhanced after treatment with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\alpha}$ and $TNF-{\gamma}$ is stronger and more rapid than $IFN-{\gamma}$ or $TNF-{\alpha}$ alone.

• Journal of Microbiology and Biotechnology
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• v.29 no.11
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• pp.1852-1859
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• 2019

Chikungunya virus (CHIKV) is a single-stranded positive-sense RNA virus, belonging to the genus Alphavirus of the Togaviridae family. It causes multiple symptoms, including headache, fever, severe joint and muscle pain, and arthralgia. Since CHIKV was first isolated in Tanzania in 1952, there have been multiple outbreaks of chikungunya fever. However, its pathogenesis and mechanisms of viral immune evasion have been poorly understood. In addition, the exact roles of individual CHIKV genes on the host innate immune response remain largely unknown. To investigate if CHIKV-encoded genes modulate the type I interferon (IFN) response, each and every CHIKV gene was screened for its effects on the induction of the IFN-β promoter. Here we report that CHIKV nsP2, E2 and E1 strongly suppressed activation of the IFN-β promoter induced by the MDA5/RIG-I receptor signaling pathway, suggesting that nsP2, E2, and E1 are the major antagonists against induction of IFN-β. Delineation of underlying mechanisms of CHIKV-mediated inhibition of the IFN-β pathway may help develop virus-specific therapeutics and vaccines.