1.Effects of Dexamethasone on expressions of IFN-gamma and IL-4 by PBMCs in response to IL-12.
Su Hak HEO ; Seong Beom LEE ; Gue Tae CHAE
Korean Leprosy Bulletin 2002;35(2):3-12
Dexamethasone is a widely used anti-inflammatory agent for a broad spectrum of diseases. The effectiveness of this agent is thought to be due to the capacity to modulate cytokine production in inflammatory cells. We examined the effects of dexamethasone on expressions of interferon gamma (IFN-gamma) and interleukin 4 (IL-4) by human peripheral blood mononuclear cells (PBMCs) in response to interleukin 12 (IL-12). Dexamethasone (10-5 M) inhibited IFN-gamma secretion, through direct suppression of IFN-gamma, IL-12 receptor (IL-12R) -beta1, and -beta2 expressions. Conversely dexamethasone increased IL-4 secretion as well as IL-4 expressions by PBMCs in response to IL-12. In addition, dexamethasone increased expression of suppressor of cytokine signalling (SOCS)-1, which inhibits JAK-STAT pathway of IL-12R signalling. The result of our study suggested that dexamethasone directly inhibited IFN-gamma expression, through suppression of IL-12 signalling and indirectly increases IL-4 expression, through suppression of IFN-gamma expression.
Dexamethasone*
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Humans
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Interferons
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Interleukin-12*
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Interleukin-4*
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Receptors, Interleukin-12
2.Increased IL-12 and Interferon-Hamma, But Not IL-18 Production, After In Vitro Stimulation with a 30-kDa Mycobacterial Antigen in Patients with Tuberculous Pleurisy.
Chang Hwa SONG ; Eun Kyeong JO ; Hwa Jung KIM ; Jae Hyun LIM ; Un Ok KIM ; Tae Hyun PAIK ; Ji Won SUHR ; Jeong Kyu PARK
Journal of the Korean Society for Microbiology 2000;35(5):358-358
No Abstract Available.
Humans
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Interleukin-12*
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Interleukin-18*
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Tuberculosis, Pleural*
3.The effect of histamine on the production of interferongamma and interleukin-12 in peripheral blood mononuclear cells from patients with atopic dermatitis.
Dou Hee YOON ; Eun Kyoung LEE ; Chung Won KIM
Journal of Asthma, Allergy and Clinical Immunology 1999;19(3):459-467
No abstract available.
Dermatitis, Atopic*
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Histamine*
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Humans
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Interleukin-12*
4.Effects of IL-12 DNA Vaccine on Reactivation of Mycobacterium tuberculosis in Cornell Model.
Bo Young JEON ; Manki SONG ; Seung Cheol KIM ; Young Cheol SUNG ; Joo Deuk KIM ; Sang Nae CHO
Journal of the Korean Society for Microbiology 2000;35(5):378-378
No Abstract Available.
DNA*
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Interleukin-12*
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Mycobacterium tuberculosis*
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Mycobacterium*
5.Requirements for the Differentiation of CD4+ Cytotoxic T cells Specific to Mycobacterial Antigens.
Chang Yong CHA ; Dong Gyun LIM ; Jung Min KIM ; Sahng June KWAK
Journal of the Korean Society for Microbiology 1997;32(3):357-368
The cytolytic activity of CD4' T cells, both human and murine, has been clearly demonstrated in the immune response to mycobacterial infection and suggested to play a significant role in the protection and immunopathology. However, Uttle is known about the differentiation of CD4' CTL. In order to address this issue, we examined the influences of some factors on the generation of CD4' CTL specific to mycobacterial antigens. After 7 days' stimulation of PBMCs from healthy tuberculin reactors with mycobacterial antigens, the cytolytic activity of purised CD4' T cells toward autologous macrophages infected with mycobacteria was measured by Cr release assay. First, we found that both of live M. tubeiculosis and soluble antigens (ST-CF) induced the cytolytic activity of CD4' T cells, although the inducibility of the former was slightly greater than the latter. Second, the cytolytic activity was maximally induced at the relatively low antigen concentration (0.2:1 bacteria:monocyte ratio or 0.5 mg/ml of ST-CF). Finally, in the presence of increasing amounts of neutralizing anti-IL-12 or anti-IFN-r MoAb, the cytolytic activity of CD4+ T cells was decreased in a dose-dependent manner. These results suggest that low dose of antigen, its particulate type give mycobacteria), IL-12, and IFN-r give some positive signals for the generation of CD4+ CTL.
Humans
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Interleukin-12
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Macrophages
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T-Lymphocytes*
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Tuberculin
6.Membrane-bound p35 Subunit of IL-12 on Tumor Cells is Functionally Equivalent to Membrane-bound Heterodimeric Single Chain IL-12 for Induction of Anti-tumor Immunity.
Hyun Jin KIM ; Sang Min PARK ; Hayyoung LEE ; Young Sang KIM
Immune Network 2016;16(5):305-310
In this study, we compared two different tumor cell vaccines for their induction of anti-tumor immunity; one was a tumor cell clone expressing a membrane-bound form of IL-12 p35 subunit (mbIL-12 p35 tumor clone), and the other was a tumor clone expressing heterodimeric IL-12 as a single chain (mb-scIL-12 tumor clone). The stimulatory effect of mb-scIL-12 on the proliferation of ConA-activated splenocytes was higher than that of mbIL-12 p35 in vitro. However, the stimulatory effect of mbIL-12 p35 was equivalent to that of recombinant soluble IL-12 (3 ng/ml). Interestingly, both tumor clones (mbIL-12 p35 and mb-scIL-12) showed similar tumorigenicity and induction of systemic anti-tumor immunity in vivo, suggesting that tumor cell expression of the membrane-bound p35 subunit is sufficient to induce anti-tumor immunity in our tumor vaccine model.
Clone Cells
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In Vitro Techniques
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Interleukin-12*
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Vaccines
7.3-Hydroxy-4,7-megastigmadien-9-one, Isolated from Ulva pertusa Kjellman, Inhibits LPS-Induced Inflammatory Response by Down-Regulating Mitogen-Activated Protein Kinase and NF-κB Pathways.
Irshad ALI ; Zahid MANZOOR ; Young Sang KOH
Journal of Bacteriology and Virology 2016;46(3):167-172
In the present study we evaluated the anti-inflammatory potential of 3-hydroxy-4,7-megastigmadien-9-one (Comp) isolated from Ulva pertusa Kjellman, in LPS-stimulated bone marrow-derived dendritic cells (BMDCs). Comp treatment exhibited strong dose dependent inhibition of IL-12 p40 and IL-6 cytokine production with IC₅₀ values of 7.85 ± 0.32 and 7.86 ± 0.18, respectively in LPS-stimulated BMDCs. Treatment of Comp inhibited MAPKs and NF-κB pathways in LPS-stimulated BMDCs by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκB. Thus, these results suggest that Comp have a significant anti-inflammatory property and affirm further studies concerning the potentials of Comp for medicinal use.
Dendritic Cells
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Interleukin-12
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Interleukin-6
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Phosphorylation
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Protein Kinases*
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Ulva*
8.Preliminary Study on the Characteristic of Plasma Cytokine Profiles in Patients with Idiopathic Multicentric Castleman Diseases.
Ning MA ; Hui-Hui LIU ; Wei LIU ; Yue YIN ; Li-Hong WANG ; Ze-Yin LIANG ; Wei-Lin XU ; Qian WANG ; Yuan LI ; Mang-Ju WANG ; Jin-Ping OU ; Wen-Sheng WANG ; Xi-Nan CEN ; Han-Yun REN ; Yu-Jun DONG
Journal of Experimental Hematology 2019;27(4):1305-1310
OBJECTIVE:
To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD).
METHODS:
The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively.
RESULTS:
Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (P<0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1β and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (P<0.01), IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (P<0.05), no significant difference of the rest cytokines was found between iMCD and the control group.
CONCLUSION
IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 、IL-21、IL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.
Castleman Disease
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Cytokines
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Humans
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Interleukin-12
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Interleukin-1beta
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Plasma
9.CD43 Expression Regulated by IL-12 Signaling Is Associated with Survival of CD8 T Cells.
Immune Network 2010;10(5):153-163
BACKGROUND: In addition to TCR and costimulatory signals, cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. METHODS: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified CD43(lo) and CD43(hi) cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. RESULTS: Compared to CD43(hi) effector cells, CD43(lo) effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. CD43(lo) effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of CD43(lo) CD8 T cells was also partly associated with CD62L expression. CONCLUSION: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.
Adoptive Transfer
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Granzymes
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Interleukin-12
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Memory
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T-Lymphocytes
10.Retroviral-mediated IL-12 gene therapy for advanced murine tumors.
Seon Hee KIM ; Chung Sun AN ; Hideaki TAHARA ; Chae Hwa PARK ; Michael T LOTZE ; Paul D ROBBINS ; Sun Young KIM
Experimental & Molecular Medicine 1997;29(1):53-58
Interleukin 12 (IL-12), a heterodimeric cytokine, promotes an effective antitumor response against tumors of various histological types when delivered systemically as a protein or locally by gene transfer. We investigated parameters that influenced the effectiveness of IL-12 retroviral-mediated gene therapy of cancer in animals using the murine breast cancer line TS/A. Syngeneic fibroblasts (TIB80), stably transduced with a retrovirus expressing murine IL-12, were used for peritumoral injection. Injection of fibroblasts into established tumors resulted in complete regression of tumor in 40 % of animals in a dose dependent manner when treated on day 4, and 20 % when treated on day 8. Significant inhibition of growth of day 21 and day 40 tumors was observed following peritumoral injection of IL-12-expressing fibroblasts in a dose-dependent manner. Delivery of IL-12 by syngeneic fibroblasts at a tumor site is effective in eradicating established, weakly immunogenic TS/A tumors.
Animals
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Breast Neoplasms
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Fibroblasts
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Genetic Therapy*
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Interleukin-12*
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Retroviridae