• Title/Summary/Keyword: B-Cell

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CD72 is a Negative Regulator of B Cell Responses to Nuclear Lupus Self-antigens and Development of Systemic Lupus Erythematosus

  • Takeshi Tsubata
    • IMMUNE NETWORK
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    • 제19권1호
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    • pp.1.1-1.13
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    • 2019
  • Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by production of autoantibodies to various nuclear antigens and overexpression of genes regulated by IFN-I called IFN signature. Genetic studies on SLE patients and mutational analyses of mouse models demonstrate crucial roles of nucleic acid (NA) sensors in development of SLE. Although NA sensors are involved in induction of antimicrobial immune responses by recognizing microbial NAs, recognition of self NAs by NA sensors induces production of autoantibodies to NAs in B cells and production of IFN-I in plasmacytoid dendritic cells. Among various NA sensors, the endosomal RNA sensor TLR7 plays an essential role in development of SLE at least in mouse models. CD72 is an inhibitory B cell co-receptor containing an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region and a C-type lectin like-domain (CTLD) in the extracellular region. CD72 is known to regulate development of SLE because CD72 polymorphisms associate with SLE in both human and mice and CD72-/- mice develop relatively severe lupus-like disease. CD72 specifically recognizes the RNA-containing endogenous TLR7 ligand Sm/RNP by its extracellular CTLD, and inhibits B cell responses to Sm/RNP by ITIM-mediated signal inhibition. These findings indicate that CD72 inhibits development of SLE by suppressing TLR7-dependent B cell response to self NAs. CD72 is thus involved in discrimination of self-NAs from microbial NAs by specifically suppressing autoimmune responses to self-NAs.

두경부 편평 세포암의 원발 병소와 전이 경부 림프절에서 Matrix Metalloproteinase-9와 Basic Fibroblast Growth Factor의 발현 (Expression of Matrix Metalloproteinase-9 and Fibroblast Growth Factor in Squamous Cell Carcinoma of the Head and Neck and Metastaric Cervical Lymph Node)

  • 노영수;황준식;김진;김진환;조성진;신형식
    • 대한두경부종양학회지
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    • 제20권1호
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    • pp.13-18
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    • 2004
  • Objectives: Cancer lethality is usually the result of local invasion and metastasis of neoplastic cell from the primary tumor. Because of their ability to degrade extracellular matrix components, matrix metalloproteinases (MMPs) and basic fibroblast growth factor (bFGF) have been implicated in the breakdown of basement membrane and underlying stroma, thereby facilitating tumor growth and invasion. It has been well established that MMPs and bFGF expression correlate with cervical lymph node metastasis, but studies on expression in the metastatic cervical lymph node itself are not enough. We have analyzed matrix metalloproteinases (MMPs) and basic fibroblast growth factor (bFGF) in squamous cell carcinoma of the head and neck and metastatic cervical lymph node, and evaluated their relationship and clinicophathologic significance. Material and Methods: 20 cases of squamous cell carcinoma of the head and neck were entered on the study of immunohistochemical stains for MMP-9 and bFGF in the obtained tissue from primary tumor and metastatic cervical lymph node. We analyzed the relationship between MMP-9, bFGF expression of the primary tumor and metastatic node with age, sex, T-stage, N-stage, histologic grade, pathologic stage and disease free survival. Results: Expression of MMP-9 and bFGF in cancer cell and metastatic lymph node was higher than that in normal cell and lymph node. According to histologic differentiation, expression of MMP-9 of the metastatic cervical lymph node was higher than primary tumor. Considering to other clinicopathologic factor, no statistical significance was seen in MMP-9 and bFGF. Conclusion: We found that expression of MMP-9 is higher in the metastatic lymph node than primary tumor in the poorly differentiated squamous cell carcinoma. But we don't find out the statistical significance in relation between bFGF and clinical factors. So we guess that some different mechanism of MMP-9 and bFGF in Head & Neck squamous cell carcinoma exist. Further studies will be necessary to establish their pathogenesis in the Head and Neck cancer.

Transient and stable expression of hepatitis B surface antigen in tomato (Lycopersicon esculentum L.)

  • Srinivas, L.;Sunil Kumar, G.B.;Ganapathi, T.R.;Revathi, C.J.;Bapat, V.A.
    • Plant Biotechnology Reports
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    • 제2권1호
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    • pp.1-6
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    • 2008
  • Cotyledonary leaves of tomato cv. Megha were transformed with the hepatitis B virus 's' gene, which encodes surface antigen. Six plant expression cassettes (pHBS, pHER, pEFEHBS, pEFEHER, pSHER and pEFESHER) were used to assay the possible expression levels by agroinfiltration. The maximum transient expression level of 489.5 ng/g D.W. was noted in pEFEHER-infiltrated cotyledonary leaves. Transgenic tomato plants with pEFEHBS and pEFEHER expression cassettes were regenerated and characterized by molecular analysis. The expression of the antigen in the fruits was confirmed by RT-PCR and ELISA analysis. This is the first report on the expression of hepatitis B surface antigen in tomato.

Regulation of the Immune System by NF-κB and IκB

  • Liou, Hsiou-Chi
    • BMB Reports
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    • 제35권6호
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    • pp.537-546
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    • 2002
  • NF-${\kappa}B$/Rel transcription factor family participates in diverse biological processes including embryo development, hematopoiesis, immune regulation, as well as neuronal functions. In this review, the NF-${\kappa}B$/Rel signal transduction pathways and their important roles in the regulation of immune system will be discussed. NF-${\kappa}B$/Rel members execute distinct functions in multiple immune cell types via the regulation of target genes essential for cell proliferation, survival, effector functions, cell trafficking and communication, as well as the formation of lymphoid architecture. Consequently, proper activation of NF-${\kappa}B$/Rel during immune responses to allergens, auto-antigens, allo-antigens, and pathogenic infection is crucial for the integrity of host innate and adaptive immunity.

Apoptotic Effects of the B Subunit of Bacterial Cytolethal Distending Toxin on the A549 Lung Cancer Cell Line

  • Yaghoobi, Hajar;Bandehpour, Mojgan;Kazemi, Bahram
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권sup3호
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    • pp.299-304
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    • 2016
  • Cytolethal distending toxin (CDT) is a secreted tripartite genotoxin produced by many pathogenic gram-negative bacteria. It is composed of three subunits, CdtA, CdtB and CdtC, and CdtB-associated deoxyribonuclease (DNase) activity is essential for the CDT toxicity. In the present study, to design a novel potentially antitumor drug against lung cancer, the possible mechanisms of cdtB anticancer properties were explored in the A549 human lung adenocarcinoma cell line. A recombinant plasmid pcDNA3.1/cdtB was constructed expressing CdtB of human periodontal bacterium Aggregatibacter actinomycetemcomitans and investigated for toxic properties in A549 cells and possible mechanisms. It was observed that plasmid pcDNA3.1/cdtB caused loss of cell viability, morphologic changes and induction of apoptosis. Furthermore, measurement of caspase activity indicated involvement of an intrinsic pathway of cell apoptosis. Consequently, the recombinant plasmid pcDNA3.1/cdtB may have potential as a new class of therapeutic agent for gene therapy of lung cancer.

두경부 편평세포암종에서 p53, p21, EGFR 및 c-erbB-2 발현의 임상적 의의 (Clinical Significance of the Expression of p53, p21, EGFR and c-erbB-2 in Squamous Cell Carcinoma of the Head and Neck)

  • 이준한;도남용;박성용;김건형;조성일
    • 대한두경부종양학회지
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    • 제21권2호
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    • pp.139-145
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    • 2005
  • Background and Objectives: Because of squamous cell carcinoma of the head and neck undergoes a generally poor hospital course, the prognostic significance of the squamous cell carcinomas in head and neck have been evaluated to identify those features associated with aggressive biologic behavior according to the immunologic and histopathologic characteristics. Materials and Method: To assess the significance of EGFR, c-erbB-2, p21 and p53 protein in head and neck tumors and their correlation with prognostic factors, samples from 74 patients with squamous cell carcinomas of larynx, pharynx, and oral cavity were studied immunohistochemically. Results: EGFR, c-erbB-2, p21, and p53 protein were expressed 94.6%, 24.3%, 85.1%, and 55.4% in 74 cases of head and neck squamous cell carcinoma, respectively. The positive expression of EGFR was associated significantly with clinical stage and the negative expressions of p21 was associated significantly with histopathologic differentiation. There were no significant relationships between the reactivity of EGFR, c-erbB-2, p21, and p53 protein. Conclusion: The expression of EGFR, c-erbB-2, p21 and p53 protein could be related to oncogenesis, and the expression of p21 and EGFR protein can be used as a prognosticator in head and neck squamous cell carcinoma under certain limitations, but c-erbB-2 and p53 protein expression alone is not enough for evaluating prognosis of the carcinoma.

Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells

  • Park, Jin-Ah;Na, Han-Heom;Jin, Hyeon-Ok;Kim, Keun-Cheol
    • Molecules and Cells
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    • 제42권12호
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    • pp.884-892
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    • 2019
  • Piperlongumine (PL), a natural alkaloid compound isolated from long pepper (Piper longum), can selectively kill cancer cells, but not normal cells, by accumulation of reactive oxygen species (ROS). The objective of this study was to investigate functional roles of expression of SETDB1 and FosB during PL treatment in MCF7 breast cancer cells. PL downregulates SETDB1 expression, and decreased SETDB1 expression enhanced caspase 9 dependent-PARP cleavage during PL-induced cell death. PL treatment generated ROS. ROS inhibitor NAC (N-acetyl cysteine) recovered SETDB1 expression decreased by PL. Decreased SETDB1 expression induced transcriptional activity of FosB during PL treatment. PARP cleavage and positive annexin V level were increased during PL treatment with FosB overexpression whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection, implying that FosB might be a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells. PL induced cell death in A549 lung cancer cells, but molecular changes involved in the induction of these cell deaths might be different. These results suggest that SETDB1 mediated FosB expression may induce cell death in PL-treated MCF7 breast cancer cells.

Cloning and Characterization of the Mycobacterium bovis BCG panB Gene Encoding Ketopantoate Hydroxymethyltransferase

  • Kim, Jin-Koo;Kim, Kwang-Dong;Lim, Jong-Seok;Lee, Hee-Gu;Kim, Sang-Jae;Cho, Sang-Hyun;Jeong, Won-Hwa;Choe, In-Seong;Chung, Thi-Wha;Paik, Sang-Gi;Choe, Yong-Kyung
    • BMB Reports
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    • 제34권4호
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    • pp.342-346
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    • 2001
  • The Mycobacterium bovis BCG panB gene, encoding ketopantoate hydroxymethyltransferase (KPHMT), was cloned from a ${\lambda}gt11$ genomic library and sequenced. The DNA sequence encodes a protein that contains 281 amino acid residues (M, 29,337) with a high similarity to the KPHMTs. Subcloning of a 846 by open reading frame (ORF), but not a 735 by ORF, into the vector pUC19 led to complementation of the panB mutant of Escherichia coli. The BCG pang gene was overexpressed in E. coli and the KPHMT purified to homogeneity The recombinant protein was further confirmed by an enzymatic assay.

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Effects of Panax ginseng on Morphine-induced Immune Suppression

  • Lee, Shee-Yong;Kim, Ae-Young;Kim, Young-Ran;Kim, Kyeong-Man
    • Biomolecules & Therapeutics
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    • 제3권3호
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    • pp.177-181
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    • 1995
  • To investigate the possibility of Panax ginseng as a therapeutic agent for the immune suppression, ginseng total saponin (GTS) extracted from korean red ginseng was tested on immune functions from morphine-induced immune suppressed mice. To study how immune functions are affected by morphine and also to test whether GTS can be an useful therapeutic agent for morphine toxicity, several parameters were employed, body weight, immune organ weight, B cell functions, and T cell function. Morphine impaired the development of body weight and immune organ weight such as spleen and thymus. Morphine also depressed a B-cell function, antibody production. T-cell functions studied by type IV hypersensitivity test were most markedly affected by morphine treatment. GTS restored most of morphine-induced immune suppression. GTS restored the morphine-induced decrease in spleen weight to body weight ratio in a dose dependent manner, but not the body weight decrease. Also all of the morphine-induced impairments of B cell functions and cellmediated immunity were fully recovered by GTS. These results suggest that ginseng product could be very helpful for the treatment of immune suppression occurring in morphine abusers.

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Cytotoxic Activities of Red Algae Collected from Jeju Island Against Four Tumor Cell Lines

  • Kim, Kil-Nam;Lee, Ki-Wan;Song, Choon-Bok;Ahn, Chang-Bum;Jeon, You-Jin
    • Preventive Nutrition and Food Science
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    • 제11권3호
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    • pp.177-183
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    • 2006
  • Methanolic and aqueous extracts of 26 red algae species collected from Jeju Island coast were prepared at a high $(70^{\circ}C)$ and a room temperature $(20^{\circ}C)$ and were examined for their cytotoxic activity against 4 tumor cell lines: U-937 (human monoblastoid leukemia cell line), HL-60 (human promyelocytic leukemia cell line), B-16 (murine melanoma cell line) and HeLa (woman cervical carcinoma cell line). $20^{\circ}C$ methanolic extract of Polysiphonia japonica showed cytotoxic activity of over 50% against U-937, HL-60 and B-16 cells. On the other hand, the $20^{\circ}C$ aqueous extract of Scinaia okamurae and $70^{\circ}C$ aqueous extract of Chondrus crispus showed cell growth inhibition activity of more than 50% against HL-60 and B-16 cells. The highest cytotoxic activity was observed in the $20^{\circ}C$ aqueous extract of Scinaia okamurae against B-16 cells (80.55%).