• The Journal of Pediatrics of Korean Medicine
• /
• v.14 no.2
• /
• pp.61-84
• /
• 2000

The purpose of this study was to investigate the effects of Kami boatang(KBT) on the immune cells in Balb/c mice. KBT (500mg/kg) was administerd p.o. once a day for 7 days. KBT enhanced the proliferation of thymocytes and splenocytes. KBT enhanced the subpopulation of helper T(Th) cells, but did not affect the subpopulation of Thyl/B220 cells and Th/Tc cells in splenocytes. KBT enhanced the production of ${\gamma}$-interferon and interleukin-2 in thymocytes, but decreased the production of interleukin-4. KBT enhanced the production of ${\gamma}$-interferon, interleukin-2 and interleukin-4 in splenocytes and serum. KBT suppressed the production of nitric oxide, and enhanced the phagocytic activity in peritoneal macrophages. These results suggest that KBT has a potent activity on the immune response via the increase of the production of cytokines and phagocytic activity in vivo.

• Molecules and Cells
• /
• v.40 no.2
• /
• pp.83-89
• /
• 2017

Error-free replication and repair of DNA are pivotal to organisms for faithful transmission of their genetic information. Cells orchestrate complex signaling networks that sense and resolve DNA damage. Post-translational protein modifications by ubiquitin and ubiquitin-like proteins, including SUMO and NEDD8, are critically involved in DNA damage response (DDR) and DNA damage tolerance (DDT). The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin. Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53,$ {\Delta}Np63{\alpha}$, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis.

• BMB Reports
• /
• v.55 no.12
• /
• pp.602-608
• /
• 2022

Uncontrolled chronic inflammation, in most cases due to excessive cytokine signaling through their receptors, is known to contribute to the development of tumorigenesis. Recently, it has been reported that the antiviral membrane protein interferon-induced transmembrane protein 3 (IFITM3), induced by interferon signaling as part of the inflammatory response after viral infection, contributes to the development of B-cell malignancy. The unexpected oncogenic signaling of IFITM3 upon malignant B cell activation elucidated the mechanism by which the uncontrolled expression of inflammatory proteins contributes to leukemogenesis. In this review, the potential effects of inflammatory cytokines on upregulation of IFITM3 and its contribution to tumorigenesis are discussed.

• Journal of Acupuncture Research
• /
• v.17 no.4
• /
• pp.28-40
• /
• 2000

Objectives : This study was purposed to investigate the effect of honey bee venom aqua-acupuncture on decreased immune response by its production from Korea, North America and China. Methods : ICR-mouse was exposed with four minute sublethal 60Co- $\gamma$ -ray irradiation onto the body and got a series of each country's 0.1 ml honey bee venom aqua-acupuncture to Choksamni(ST36) every other day for three times. Thereafter the numbers of WBC, delayed type hypersensitivity, hemagglutinin titers, hemolysin titers, quantitation of T-cell and B-cell, lymphocyte transformation, natural killer cell activity, interleukin-2 productivity and interferon productivity were measured. Results : The numbers of WBC, delayed type hypersensitivity, hemagglutinin titers, hemolysin titers, quantitation of T-cell and B-cell and lymphocyte transformation were increased respectively with statistical significance in Korean, North American and Chinese honey bee venom aqua-acupuncture groups as compared with the control group. The natural killer cell activity was increased with statistical significance in Korean honey bee venom aqua-acupuncture group, and Interleukin-2 productivity and interferon productivity were not shown any statistical significance in all experimental groups as compared with the control group. Conclusions : According to the results, honey bee venom aqua-acupuncture has significant effect on decreased immune response, and Korean bee venom can be substituted for North American and Chinese one.

• Asian-Australasian Journal of Animal Sciences
• /
• v.23 no.8
• /
• pp.1089-1095
• /
• 2010

Four biological candidate genes, natural resistance associated macrophage protein 1 (SLC11A1 or NRAMP), prosaposin (PSAP), interferon Gamma (IFNG), and toll-like receptor 4 (TLR4), were examined to identify single nucleotide polymorphisms (SNP) and associations of the SNP with antibody response kinetics in hens. An $F_2$ population was produced by mating $G_0$ highly inbred (<99%) males of two MHC-congenic Fayoumi lines with highly inbred Leghorn hens. The $F_2$ hens (n = 158) were injected twice with SRBC and whole, fixed Brucella abortus (BA). Blood samples were obtained before each immunization, at 7 d after primary immunization, and at several time points after secondary immunization. Minimum titers (Ymin) and the time needed to reach them (Tmin), and maximum (Ymax) titers and the time needed to reach them (Tmax), were estimated from the seven post-secondary immunization titers using a nonlinear regression model. The $F_2$ hens were genotyped for the four candidate genes by using PCR-RFLP for one SNP per gene, which identified the parental allele. General linear models were used to test associations of SNP genotypes with antibody response parameters and BW measured at 4 ages. The IFNG SNP was highly significantly (p<0.0125) associated with primary response to SRBC, Tmin to BA, Ymin to BA, and 12-week BW. The current study demonstrated that the novel IFNG promoter SNP was associated with antibody kinetics for BA and SRBC in laying hens, and also with BW, suggesting that this cytokine may play a pivotal role in the relationship between immune function and growth.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.5
• /
• pp.943-947
• /
• 2002

The purpose of this research was to investigate the effects of Bojunglkgi-tang water extract (BE) on the specific immune response in BALB/c mice. When BE (500mg/kg) was administerd p.o. once a day for 7 days to BALB/c mice, the cell viability of splenocytes was increased and DNA fragmentation of splenocytes was decreased. But, BE did not affect the cell viability and DNA fragmentation of thymocytes. Also, BE increased the population of Thy1/sup +/ cells and TH cells in splenocytes. In addition, BE increased the production of γ -interferon from splenocytes. These results suggest that BE enhances the specific immune response via activation of TH1 cells in splenocytes.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.23 no.5
• /
• pp.986-992
• /
• 2009

Type I interferons (IFNs) are critical mediators of the innate immune system to defend viral infection. Interferon regulatory factor (IRF) and signal transducer and activator of transcription (STAT) play critical roles in type I IFN production in response to viral infection. Luteolin is natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anti-carcinogenic effects. However, the mechanism of action and impact of luteolin on innate immunity is still unknown. In this study, we examined the effects of luteolin on the lipopolysacchride (LPS)-induced inflammatory responses. Luteolin inhibited Type I IFNs expression of mRNA and increased interleukin(IL)-10 expression of mRNA. Next, we examined the protective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action didn't cause a significant reduction of Type I IFNs than LPS-induced luteolin pretreatment. Pretreatment of luteolin inhibited the level of IRF-1, and IRF-7 mRNA and the nuclear translocation of IRF-3. Also, luteolin reduced the activation of STAT - 1, 3. Theses results suggest that luteolin inhibits LPS-induced the production of Type I IFNS by both IRFs and STATs not IL-10 and may be a beneficial drug for the treatment of inflammatory disease.

• The Journal of the Korean Society for Microbiology
• /
• v.14 no.1
• /
• pp.79-87
• /
• 1979

The immunosuppressive activity of newcastle disease virus(NDV) and some possible role of interferon(C-IF) in viral suppression of immune response were evaluated by SRBC-induced delayed-type hypersensitivity(DTH), rosette formation in spleen cells, number of lymphocytes in peripheral blood, hemagglutinin and hemolysin response to SRBC in ICR mice sensitized with SRBC. When NDV was inoculated before or after sensitization of mouse with SRBC, virus caused a marked inhibition of DTH, and its depressive effect was dependent on the time of virus inoculation in relation to SRBC sensitization or challenge. Rosette formation of spleen cells was significantly reduced by NDV infection. The degree of the depression of rosette formation was more prominent in mice inoculated before sensitization than after sensitization and could be related to the amount of serum interferon induced by the virus. Humoral response to SRBC of virus infected mouse was significantly depressed when NDV was inoculated 24 or 48 hours before sensitization. However, there was no difference in the response when the virus was inoculated 9 hour before and at the same time of sensitization or even after that. Lymphocytes in peripheral blood of mice were markedly diminished in numbers when NDV was inoculated 48 and 24 hour before sensitization with SRBC, but they were slightly augmented when the virus was inoculated 9 hour before and at the same time of sensitization. When UV-inactivated or heat-inactivated NDV was injected to the mouse at the same time of sensitization with SRBC, DTH and rosette formation of spleen cells were slightly depressed. DTH and rosette formation in mice treated with crude-IF were generally depressed as com pared with those of control mice. These studies suggest that the NDV causes a significant depression of cell-mediated immunity, whereas the humoral immune response is not inhibited markedly, and that the depression of immune response by NDV infection may be caused by interferon produced by NDV and direct viral activity.

• BMB Reports
• /
• v.52 no.5
• /
• pp.336-341
• /
• 2019

The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon ($IFN-{\alpha}$), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines.

• BMB Reports
• /
• v.56 no.5
• /
• pp.314-319
• /
• 2023

Sepsis is a life-threatening multi-organ dysfunction with high mortality caused by the body's improper response to microbial infection. No new effective therapy has emerged that can adequately treat patients with sepsis. We previously demonstrated that interferon-β (IFN-β) protects against sepsis via sirtuin 1-(SIRT1)-mediated immunosuppression. Another study also reported its significant protective effect against acute respiratory distress syndrome, a complication of severe sepsis, in human patients. However, the IFN-β effect cannot solely be explained by SIRT1-mediated immunosuppression, since sepsis induces immunosuppression in patients. Here, we show that IFN-β, in combination with nicotinamide riboside (NR), alleviates sepsis by blocking endothelial damage via SIRT1 activation. IFN-β plus NR protected against cecal ligation puncture-(CLP)-induced sepsis in wild-type mice, but not in endothelial cell-specific Sirt1 knockout (EC-Sirt1 KO) mice. IFN-β upregulated SIRT1 protein expression in endothelial cells in a protein synthesis-independent manner. IFN-β plus NR reduced the CLP-induced increase in in vivo endothelial permeability in wild-type, but not EC-Sirt1 KO mice. IFN-β plus NR suppressed lipopolysaccharide-induced up-regulation of heparinase 1, but the effect was abolished by Sirt1 knockdown in endothelial cells. Our results suggest that IFN-β plus NR protects against endothelial damage during sepsis via activation of the SIRT1/heparinase 1 pathway.