• The Korean Journal of Physiology and Pharmacology
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• 제20권5호
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• pp.515-523
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• 2016

Adhesion events of monocytes represent an important step in inflammatory responses induced by chemokines. The ${\beta}1$-integrin CD29 is a major adhesion molecule regulating leukocyte migration and extravasation. Although several adhesion molecules have been known as regulators of CD29, the molecular interactions between CD29 and its regulatory adhesion molecules (such as CD98 and CD147) have not been fully elucidated. Therefore, in this study, we examined whether these molecules are functionally, biochemically, and cell-biologically associated using monocytic U937 cells treated with aggregation-stimulating and blocking antibodies, as well as enzyme inhibitors. The surface levels of CD29, CD98, and CD147 (but not CD43, CD44, and CD82) were increased. The activation of CD29, CD98, and CD147 by ligation of them with aggregation-activating antibodies triggered the induction of cell-cell adhesion, and sensitivity to various enzyme inhibitors and aggregation-blocking antibodies was similar for CD29-, CD98-, and CD147-induced U937 cell aggregation. Molecular association between these molecules and the actin cytoskeleton was confirmed by confocal microscopy and immunoprecipitation. These results strongly suggest that CD29 might be modulated by its biochemical and cellular regulators, including CD98 and CD147, via the actin cytoskeleton.

• BMB Reports
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• 제47권5호
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• pp.241-248
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• 2014

CD1 molecules belong to non-polymorphic MHC class I-like proteins and present lipid antigens to T cells. Five different CD1 genes (CD1a-e) have been identified and classified into two groups. Group 1 include CD1a-c and present pathogenic lipid antigens to ${\alpha}{\beta}$ T cells reminiscence of peptide antigen presentation by MHC-I molecules. CD1d is the only member of Group 2 and presents foreign and self lipid antigens to a specialized subset of ${\alpha}{\beta}$ T cells, NKT cells. NKT cells are involved in diverse immune responses through prompt and massive production of cytokines. CD1d-dependent NKT cells are categorized upon the usage of their T cell receptors. A major subtype of NKT cells (type I) is invariant NKT cells which utilize invariant $V{\alpha}14-J{\alpha}18$ TCR alpha chain in mouse. The remaining NKT cells (type II) utilize diverse TCR alpha chains. Engineered CD1d molecules with modified intracellular trafficking produce either type I or type II NKT cell-defects suggesting the lipid antigens for each subtypes of NKT cells are processed/generated in different intracellular compartments. Since the usage of TCR by a T cell is the result of antigen-driven selection, the intracellular metabolic pathways of lipid antigen are a key in forming the functional NKT cell repertoire.

• 약학회지
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• 제50권4호
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• pp.263-267
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• 2006

CD1d is an unique antigen presenting molecule which provides antigenic repertoires to NKT cells. To examine molecules required for CD1d antigen presentation, we determined an interaction between CD1d and several endoplasmic reticulum (ER) resident molecular chaperones by co-immunoprecipitation. Results indicated that calnexin and calreticulin seem to be bound to mouse CD1d, but TAP and tapasin do not bind. Further, we screened an yeat two hybrid system to identify proteins that help mouse CD1d transportation in the cytosol. We found that two proteins, heat shock protein a sub-unit $(Hsp90{\alpha})$ and protein kinase C and casein kinase substrate in neurons 3 (PACSIN-3), interact with CD1d. Future study will be focus on the role of these molecules during the CD1d antigen presentation.

• IMMUNE NETWORK
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• 제5권2호
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• pp.68-77
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• 2005

Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

• Bulletin of the Korean Chemical Society
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• 제19권11호
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• pp.1222-1227
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• 1998

The crystal structure of a benzene sorption complex of fully dehydrated Cd2+-exchanged zeolite X, Cd46Si100Al92O384·43C6H6 (a=24.880(6) Å), has been determined by single-crystal X-ray diffraction techniques in the cubic space group Fd3 at 21 ℃. The crystal was prepared by ion exchange in a flowing stream of 0.05 M aqueous Cd(NO3)2 for 3 d, followed by dehydration at 400 ℃ and 2 x 10-6 Torr for 2 d, followed by exposure to about 92 Torr of benzene vapor at 22 ℃. The structure was determined in this atmosphere and refined to the final error indices R1=0.054 and Rw=0.066 with 561 reflections for which I > 3σ(I). In this structure, Cd2+ ions are found at four crystallographic sites: eleven Cd2+ ions are at site 1, at the centers of the double six-oxygen rings; six Cd2+ ions lie at site I', in the sodalite cavity opposite to the double six-oxygen rings; and the remaining 29 Cd2+ ions are found at two nonequivalent threefold axes of unit cell, sites Ⅱ' (in the sodalite cavity ) and site Ⅱ (in the supercage) with occupancies of 2 and 27 ions, respectively. Each of these Cd2+ ions coordinates to three framework oxylkens, either at 2.173(13) or 2.224(10) Å, respectively, and extends 0.37 Å into the sodalite unit or 0.60 Å into the supercage from the plane of the three oxygens to which it is bound. The benzene molecules are found at two distinct sites within the supercages. Twenty-seven benzenes lie on threefold axes in the large cavities where they interact facially with the latter 27 site-Ⅱ Cd2+ ions (Cd2+-benzene center=2.72 Å; occupancy=27 molecules/32 sites). The remaining sixteen benzene molecules are found in 12ring planes; occupancy=16 molecules/16 sites. Each hydrogen of these sixteen benzenes is ca. 2.8/3.0 Å from three 12-ring oxygens where each is stabilized by multiple weak electrostatic and van der Waals interactions with framework oxygens.

• BMB Reports
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• 제54권1호
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• pp.2-11
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• 2021

Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy.

• IMMUNE NETWORK
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• 제1권1호
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• pp.36-44
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• 2001

Background : Peritoneal metastasis is one of the maj or types of the stomach cancer recurrence and the role of the adhesion molecules is thought to be very much important in this event. Retinoic acid (RA) has been known to induce the growth inhibition and differentiation of various malignancies, and apoptpsis and the change of expression of adhesion molecules have been reported to be involved in the action of RA. Methods : We studied the adhesion abilities of SNU-1, SNU-5, and SNU-6 cells to the peritoneal endothelial cells as well as the expression of the adhesion molecules (CD44, ICAM-1) in Western blot analysis. And also we studied the expression of apoptosis and the change of expression patterns of the various isoforms of CD44 and the change of the adhsion abilities of the cell line cells after RA treatment. Results: CD44 was expressed in SNU-5 and -16, together with an isoform in SNU-16. ICAM-1 was not expressed in any of the cell line cells tested. After the treatment of RA in the concentration range of $1-5{\times}10^{-5}M$ to three stomach cancer cell lines, growth inhibition, apoptosis and the change of expression of the CD44 were noted. After RA treatment, the expression of CD44H was weakly increased in SNU-1, and was markedly increased in SNU-5. In SNU-16, the expression of CD44H was decreased while that of CD44E were markedly increased. The adhesibility of cells to peritoneal cells was increased in relation with the increase of the CD44H expression, which shows the fact that the adhesibility of tumor cells to peritoneal mesothelial cells is mediated by CD44H recognizing hyaluronic acid. Conclusion : RA induces growth inhibition of stomach cancer cell line cells and increase the adhesiblity of stomach cancer cell line cells to peritoneal mesothelium. It is believed that RA decreases the metastatic ability of stomach cancer cells by upregulating the CD44H expression.

• 약학회지
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• 제52권5호
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• pp.412-417
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• 2008

BAY11-7082 was initially found to be an anti-inflammatory drug with NF-${\kappa}B$ inhibitory property. In this study, we evaluated modulatory function of BAY11-7082 on U937 cell-cell adhesion induced by CD29 (${\beta}1$-integrins). BAY11-7082 strongly blocked functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay. However, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. In particular, to understand molecular mechanism of BAY11-7082-mediated inhibition, the regulatory roles of CD29-induced actin cytoskeleton rearrangement under cell-cell adhesion and surface level of CD29 were examined using confocal and flow cytometic analysis. Interestingly, this compound strongly suppressed the molecular association of actin cytoskeleton with CD29 at cell-cell adhesion site. Moreover, BAY11-7082 also diminished surface levels of CD29 as well as its-associated adhesion molecule CD147, but not other adhesion molecules such as CD18 and CD43. Therefore, our data suggest that BAY11-7082 may be involved in regulating immune responses managed by CD29-mediated cell-cell adhesion.

• Animal cells and systems
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• 제8권2호
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• pp.125-133
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• 2004

We have extended our previous work that cross-linking CD4 molecules using specific MAb induced antigen nonspecific, MHC unrestricted killing of virally infected target cells by CD$4^+$We have extended our previous work that cross-linking CD$4^+$ molecules using specific MAb induced antigen nonspecific, MHC unrestricted killing of virally infected target cells by CD$4^+$ T cells. The killing activity of antibody activated CD$4^+$T cells was completely blocked by herbimycin A, a protein tyrosine kinase (PTK) inhibitor, but not by bisindolylamaleimide, a protein kinase C (PKC) inhibitor. Herbimycin A treated human or bovine peripheral blood CD$4^+$T cells lacked PTK activity and failed to kill virally infected target cells even after cross-linking of CD4 molecules. The CD$4^+$cross-linking failed to induce effector cell proliferation or the transcription of TNF${\beta}$ Upregulation of TNF${\beta}$ was induced by incubating the antibody activated effector cells with BHV-1 infected D17 target cells for 10 h. Anti-TNF${\beta}$ antibody partially abolished (13-44%) the direct effector cell-mediated antiviral cytotoxicity. However, this antibody neutralized 70 to 100% of antiviral activity of effector and target cell culture supernatants against BHV-1 infected D17 cells. The inhibition level of the antiviral activity by the antibody was dependent on the effector and target cell ratio. These results support the hypothesis that increased p$56^ICK enzyme activity in effector cells transduces a signal critical for effector cell recognition of viral glycoproteins expressed on the target cells. Following target cell recognition, lytic cytokines known to participate in target cell killing were produced. A better understanding of the killing activity displayed by CD$4^+$T lymphocytes following surface receptor cross-linking will provide insight into the mechanisms of cytotoxic activity directed toward virally-infected cells.T cells. The killing activity of antibody activated CD$4^+$T cells was completely blocked by herbimycin A, a protein tyrosine kinase (PTK) inhibitor, but not by bisindolylamaleimide, a protein kinase C (PKC) inhibitor. Herbimycin A treated human or bovine peripheral blood CD4T cells lacked PTK activity and failed to kill virally infected target cells even after cross-linking of CD4molecules. The CD4 cross-linking failed to induce effector cell proliferation or the transcription of TNF$\beta$. Upregulation of TNF$\beta$ was induced by incubating the antibody activated effector cells with BHV-1 infected D17 target cells for 10 h. Anti-TNF$\beta$ antibody partially abolished (13-44%) the direct effector cell-mediated antiviral cytotoxicity. However, this antibody neutralized 70 to 100% of antiviral activity of effector and target cell culture supernatants against BHV-1 infected D17 cells. The inhibition level of the antiviral activity by the antibody was dependent on the effector and target cell ratio. These results support the hypothesis that increased $56^ICK enzyme activity in effector cells transduces a signal critical for effector cell recognition of viral glycoproteins expressed on the target cells. Following target cell recognition, lytic cytokines known to participate in target cell killing were produced. A better understanding of the killing activity displayed by CD$4^+$T lymphocytes following surface receptor cross-linking will provide insight into the mechanisms of cytotoxic activity directed toward virally-infected cells.

• 약학회지
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• 제51권6호
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• pp.482-489
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• 2007

Kaempferitrin, isolated from Kenaf (Hibiscus cannabinus), was examined to evaluate its modulatory effects on antigen-presenting cell functions of macrophages/monocytes such as phagocytosis of foreign materials, up-regulation of costimulatory molecules (CD40, CD80 and CD86), adhesion molecule activation, and antigen processing and presentation. Kaempferitrin strongly blocked up-regulation of CD40, CD80 and CD86, but not pattern recognition receptor (PRR) (e.g., TLR2). It also suppressed functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay, required for T cell-antigen-presenting cell (APC) interaction. Furthermore, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. However, the compound did not diminish phagocytic uptake, an initial step for antigen processing, and ROS generation in RAW264.7 cells. In particular, to understand molecular mechanism of kaempferitrin-mediated inhibition, the regulatory role of LPS-induced signaling events was examined using immunoblotting analysis. Interestingly, this compound dose dependently suppressed the phosphorylation of $I{\kappa}B{\alpha}$, Src, Akt and Syk, demonstrating that it can negatively modulate the activation of these signaling enzymes. Therefore, our data suggested that kaempferitrin may be involved in regulating APC function-relevant immune responses of macrophages and monocytes by regulating intracellular signaling.