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CD74 is a survival receptor on colon epithelial cells

World Journal of Gastroenterology 2010年第26期16卷 3258-3266页

作者： Nitsan Maharshak Sivan Cohen Frida Lantner Gili Hart Richard Bucala Idit Shachar Department of Immunology Weizmann Institute of Science Rehovot 76100 Israel Department of Gastroenterology and Liver Diseases Tel Aviv Sourasky Medical Center Affiliated to the Sackler Faculty of Medicine Tel Aviv University Tel Aviv 69978 Israel Department of Medicine Yale University School of Medicine New Haven CT 06520 United States

AIM: To investigate the expression and function of CD74 in normal murine colon epithelial cells (CEC) and colon carcinoma cells. METHODS: Expression of CD74 mRNA and protein were measured by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and fluorescence-activated cell sorter (FACS). The effect of migration inhibitory factor (MIF) on the survival of normal CEC from C57BL/6, NOD/SCID, and CD74 def icient mice both in vitro and in vivo, and on the CT26 carcinoma cell line was analyzed by (quantitative) qRT-PCR, RTPCR, Western blotting and FACS. RESULTS: CD74 was found to be expressed on normalCEC. Stimulation of CD74 by MIF induced a signaling cascade leading to up-regulation of Bcl-2 expression, resulting in a signif icant increased survival of CEC. CD74 was also expressed on the CT26 colon carcinoma cell line and its stimulation by MIF resulted in enhanced cell survival, up-regulation of Akt phosphorylation and Bcl-2 expression.

关键词： CD74 Migration inhibitory factor colon epithelial cells

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Identification of a Native Novel Oncolytic Immunoglobulin on Exfoliated colon epithelial cells: A Bispecific Heterodimeric Chimera of IgA/IgG*

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Open Journal of Preventive Medicine 2020年第6期10卷 126-150页

作者： George P. Albaugh Sudhir K. Dutta Vasantha Iyengar Samina Shami Althaf Lohani Eduardo Sainz George Kessie Prasanna Nair Sara Lagerholm Alka Kamra J.-H. Joshua Chen Shilpa Kalavapudi Rakesh Vinayek Robert Shores Laila E. Phillips Ram Nair Padmanabhan P. Nair Beltsville Human Nutrition Research Centre Agricultural Research Service Beltsville MD USA Division of Gastroenterology Sinai Hospital of Baltimore Baltimore MD USA Department of International Health Johns Hopkins University Bloomberg School of Public Health Baltimore MD USA NonInvasive Technologies LLC Elkridge MD USA Department of Pediatrics University of Maryland School of Medicine Baltimore MD USA

Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.

关键词： colon epithelial cells CXCR-4 IgA/IgG Chimeric Immunoglobulin Heterodimer COX-2 LGR-5 Musashi-1 Dedifferentiation Cellular Engraftment Oncoly-sis Gastrointestinal Progenitor Stem cells (GIP-C)

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A 75 kDa glycoprotein isolated from Cudrania tricuspidata Bureau induces colonic epithelial proliferation and ameliorates mouse colitis induced by dextran sulfate sodium

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Chinese Journal of Natural Medicines 2021年第1期19卷 46-55页

作者： Park Jeong-Bae Kim Do-Wan Lim Kye-Tack Oh Sejong Lee Sei-Jung Department of Pharmaceutical Engineering Daegu Haany UniversityGyeongsan 38610South Korea Division of Animal Science Chonnam National UniversityGwangju 61186South Korea

Cudrania tricuspidata Bureau(CTB),a species of the Moraceae plant,has been used as a bruise recovery *** study aimed to determine whether the 75 kDa phytoglycoprotein extracted from CTB has a regulatory effect on the proliferation of human colon epithelial cells and the pathological process of inflammatory bowel disease(IBD).We found that CTB glycoprotein significantly induces the proliferation of human colon epithelial HT-29 cells by activating protein kinase *** glycoprotein stimulated the phosphorylation of c-Jun N-terminal kinase and transcription factor nuclear factor-κB,which are responsible for the expression of cell-cycle-related proteins(CDK2,CDK4,cyclin D1 and cyclin E)during its promotion of cell *** colitis was induced in mice by adding dextran sulfate sodium to their drinking water at a concentration of 4%(W/V)for seven *** found that CTB glycoprotein ameliorates the pathological process of IBD and lowers the disease activity index score,which was composed of body weight change,diarrhea,and hematochezia in ICR mice treated with dextran sulfate ***,we suggest that CTB glycoprotein has the ability to prevent IBD by promoting cell proliferation signaling events via the activation of PKC,JNK and NF-κB in colon epithelial cells.

关键词： Cell cycle Cell proliferation colon epithelial cells Cudrania tricuspidata Glycoprotein Inflammatory bowel disease Protein kinase C

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Germline Deletion of the Expression of a Human Bispecific Mucosal Immunoglobulin: Genetic Predisposition to Cancer and Communicable Diseases Predominantly among African-Americans

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Open Journal of Preventive Medicine 2021年第10期11卷 383-390页

作者： Padmanabhan Nair NonInvasive Technologies LLC Elkridge MD USA Department of International Health The Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA

In a previous report we had reported on the discovery of a novel bispecific immunoglobulin expressed by colonic epithelial cells as they transform into immunomimetic cells during exfoliation (Albaugh et al. (2020) Open Journal of Preventive Medicine, 10, 126-150). colonic cells isolated from 0.5 gm aliquots of fresh stools (SCSR-10, Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD) preserved at room temperature for up to one week, with viability of >85% were used to determine the number of cells expressing this novel bispecific immunoglobulin. Over the course of this period (18 years) we recognized that these cells opened the opportunity to investigate the expression of cell membrane biomarkers. As the applications grew, we introduced a new terminology, termed COPROCYTOBIOLOGY*. In this study, we surveyed a cohort of 58 free-living adults for the expression of the newly discovered bi-specific chimeric antibody. Almost all of the subjects showed a strong signal during flow-cytometric evaluation of their stool samples;averaging around 65%. However, two subjects exhibited a total loss of this signal and both these individuals were of African-American lineage (one male and one female). These cells upon culturing in vitro remained defective in contrast to the rest of the group where their progeny continued to generate the antibody. We propose that this signals the existence of a germ-line deletion of the gene for which a novel test (MEDISHIELD†) is suggested. This syndrome may be associated with a lack of response to prophylactic vaccines involving m-RNA.

关键词： colon epithelial cells IgA/IgG Bi-Specific Immunoglobulin Oncolysis Anti-Infective Firewall Heterodimer Gastrointestinal Progenitor cells (GIP-C†)

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