• Archives of Pharmacal Research
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• 제17권3호
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• pp.194-198
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• 1994

The antitumor effects of the 2E4 and anti--Tac, monoclonal antibodies directed to Il-2 receptor (IL-2R) conjugated with .alpha.-particle emitting radionuclide bismuth-212., were compared. The $^{212}Bi-2E4$ demonstratedspecific cytotocicity to EL4J3, 4, a I$L-2R^+$ cell line, than to EL4J, a $IL-2R^-$ cell line in thymidine incorporation assy. TEX>$^{212}Bi-2E4$ exerted the maximal antitumor effect in that % T/C in C57BL/6 mice implanted with EL4J3.4 ascitic tumor was 331% at the concentration of $50{\;}{\mu}Ci$, while that of $^{212}Bi-anti-Tac$ was 258% at $100{\;}{\mu}Ci$.

• IMMUNE NETWORK
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• 제2권2호
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• pp.72-78
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• 2002

Background: The precise mechanism by which CTLA-4 regulates T cell immune responses is still not fully understood. Previously we proposed that CTLA-4 could downregulate T cell function by modulating a signaling cascade initiated from the T cell receptor complex. The evidence for this notion comes from our findings that CTLA-4 associated with the T cell receptor zeta (TCR zeta) chain, and hence regulated TCR zeta phosphorylation by co-associated SHP-2 tyrosine phosphatase (1). In this report, we investigated whether any other signaling molecules could be involved in the CTLA-4 signaling pathway. Methods: We have taken biochemical approaches, such as immunoprecipitation followed by autoradiography or immunoblotting, to identify the molecules associated with CTLA-4. To perform these assays, we used activated primary T cells and ectopically transfected 293 cells. Various truncation mutants of CTLA-4 were used to map the interaction site on CTLA-4. Results: We found that in addition to TCR zeta and SHP-2, a recently cloned small adaptor molecule, SAP (SLAM-associated protein), was also able to associate with CTLA-4. We identified the domain of SAP association in CTLA-4 being a motif involving GVYVKM. This motif has been previously found to bind SHP-2 through its phosphorylated tyrosine interaction with SH-2 domain of SHP-2. Indeed, co-expression of SAP and SHP-2 reduced their binding to CTLA-4 significantly, suggesting that SAP and SHP-2 compete for the common binding site, GVYVKM. Thus, by blocking SHP-2 recruitment SAP could function as a negative regulator of CTLA-4. Conclusion: Taken together, our data suggest the existence of complicate signaling cascade in regulating CTLA-4 function, and further provide evidence that SAP can act either as a positive or negative regulator depending on the nature of the associating receptors.

• 동국한의학연구소논문집
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• 제5권
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• pp.197-207
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• 1996

As a mood-altering drug, long-term alcohol consumption have significant harmful effects on the human body and people's mental functioning. This study observed that the suppression of cell mediated immunity induced in spleen of ICR mouse by long-term alcohol administration. After 8% alcohol voluntary administered for 120 days, the splenic tissue irnmunohistochemically stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly-2(CD8), IL-2 receptor(CD25R) and NK-1.1(CD56) after embedding with paraffin. The results were as follows. 1. The size of marginal zone in splenic white pulp was diminished and the number of macrophage in marginal zone was decreased in test group than control group. 2. After alcohol administration, the number of Helper T lymphocyte, cytotoxic T lymphocyte, and IL-2 receptor were decreased in periarterial lymphatic sheaths of white pulp and penicilla artery of red pulp and the degree of CD4, CD8, and CD25R positive reaction were soften. 3. In test group, the number of NK cell were decreased. These results indicated that the secretion of lymphokine as IL-2 was inhibited by long-term alcohol administration and subsequently prevent to activate and proliferate splenic T lymphocytes and NK cells as cell mediated immunity component.

• IMMUNE NETWORK
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• 제5권1호
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• pp.23-29
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• 2005

Background: Interleukin-7 receptor (IL-7R) ${\alpha}$-deficient mice have small numbers of B cells and ${\alpha}{\beta}$T cells in periphery, they totally lack ${\gamma}{\delta}$T cells. In addition, the V-J recombination and transcription of TCR ${\gamma}$ genes is also severely impaired in IL-7R ${\alpha}$-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCR ${\gamma}$ locus, and promotes V-J recombination and ${\gamma}{\delta}$T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic ${\gamma}{\delta}$T cell development are largely unknown. Methods: To clarify the role of the IL-7 receptor in proliferation and survival of ${\gamma}{\delta}$T cells, we introduced the TCR ${\gamma}{\delta}$ transgene, $V_{{\gamma}2}/V{\delta}_5$, into IL-7R ${\alpha}$-deficient mice, and investigated the development of ${\gamma}{\delta}$T cells. Results: We found that $V_{{\gamma}2}/V{\delta}_5$ transgene restored ${\gamma}{\delta}$T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of ${\gamma}{\delta}$T cells in the thymus and the spleen of these mice. Conclusion: Taken together, this study revealed that the IL-7R ${\alpha}$ is indispensable for proliferation and survival mainly in thymic ${\gamma}{\delta}$T cell development.

• Parasites, Hosts and Diseases
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• 제49권3호
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• pp.235-243
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• 2011

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.322-327
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• 2018

A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.

• Molecules and Cells
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• 제42권12호
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• pp.869-883
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• 2019

Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4⁺ T, CD8⁺ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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• pp.209-214
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• 2005

Immunoglobulins (IG) , T cell receptors (TR) and major histocompatibility complex (MHC) are major components of the immune system. Their experimentally determined three-dimensional (3D) structures are numerous and their retrieval and comparison is problematic. IMGT, the international ImMunoGeneTics information system$^{\circledR}$(http://imgt.cines.fr), has devised controlled vocabulary and annotation rules for the sequences and 3D structures of the IG TR and MHC. Annotated data from IMGT/3D sructure-DB, the IMGT 3D structure database, are used in this paper to compare 3D structure of the domains and receptor, and to characterize IG/antigen, peptide/MHC and TR/peptide/MHC interfaces. The analysis includes angle measures to assess receptor flexibility, structural superimposition and contact analysis. Up-to-date data and analysis results are available at the IMGT Web site, http://imgt.cines.fr.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.655-660
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• 2023

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

• 동의신경정신과학회지
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• 제7권1호
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• pp.49-63
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• 1996

After applying the gravity acceleration stress to a mice, the effect on organ index was examined, and the Con A stimulating proliferation rate of splenocytes, expression of IL-2 receptor and T cell subsets of thymocytes were analyzed and also clearance of C. neoformans was measured. The results were as follows :1. Form finding the organ index after 4 days stress, the indexes of the spleen and thymus were reduced in the res group exposed to the gravity acceleration.2. From finding the proliferation rate by stimulating the splenocytes with Con 4 after 7 days stress, the proliferation rates were all reduced in the stress group, the Yangsimtang group, and the stress and Yangsimtang group. 3. The expression of IL-2 receptor in resting stage was reduced, comparing to the test group, both in the stress group and the Yangsimtang group, however, comparing to the stress group, it was somewhat recovered in the stress and Yangsimtang group.4. To see the IL-2 receptor driven-out after being stimulated by Con-A, the expression of IL-2 receptor was all reduced in the stress group, the Yangsimtang group, and the stress and Yangsimtang group.5. To the rate of T cell subsets of thymus, there's no difference, comparing to the test group, in the Yangsimtang group, however, the rate of $CD4^+CD8^-,\;CD4^-CD8^+,\;and\;CD4^-CD8^-$ cell was significantly reduced in the stress group. And, the $CD4^+CD8^+$ which had been reduced by stress was somewhat recovered in the stress and Yangsimtang group.6. To the effect on the clearance of C, neoformans infection, the numbers of fungi detected at the spleen was, comparing to the test group, increased by 12.6 tines in the Yangsimtang group.