Ngan, Kit Shan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 176-187). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Thesis (Ph. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains xv, 190 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

Thesis (M.S.)--University of Missouri--Columbia, 2004. / Typescript. Includes bibliographical references (leaves 97-111). Also issued on the Internet.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 1999. / Typescript. Bibliography: leaves 113-124.

Besides the molecular mechanisms regulating activation of FLS mentioned above, we also investigated anti-inflammatory activities of Chinese herbal medicine sinomenine and Liang Miao San on activated human FLS in RA. Sinomenine, an alkaloid isolated from the root of Sinomenium acutum, has been used to alleviate the symptoms of rheumatic diseases. Liang Miao San (LMS), composed of the herbs Rhizoma Atractylodis (Cangzhu) and Cotex Phellodendri (Huangbai), is another traditional Chinese medicine formula for RA treatment. Since the potential anti-inflammatory activities of sinomenine and LMS have been demonstrated, we investigated the in vitro anti-inflammatory effects of sinomenine and LMS on inflammatory cytokine TNF-alpha activation of human normal and RA-FLS and the underlying intracellular mechanisms. In the present study, sinomenine was found to significantly inhibit TNF-alpha induced cell surface expression of VCAM-1 and release of inflammatory cytokine and chemokine IL-6, CCL2 and CXCL8 from both normal and RA-FLS (all p < 0.05). Our results provide a new insight into the differential anti-inflammatory activities of sinomenine and LMS through the suppression of TNF-alpha activated FLS by modulating distinct intracellular signaling pathways in RA, and help to provide a biochemical basis for the development of a cost-effective human synoviocyte model for the future screening of traditional Chinese medicine (TCM) possessing potential anti-rheumatic activities. (Abstract shortened by UMI.) / IL-27, a novel member of the IL-12 family that is produced early by antigen-presenting cells (APCs), can promote T cell proliferation as well as the production of interferon-gamma by naive T lymphocytes. Recent studies have found that elevated expression of IL-27 has been detected in the synovial membranes and fluid of RA. Herein we investigated the in vitro effects of IL-27, alone or in combination with inflammatory cytokine TNF-alpha or IL-Ibeta on the pro-inflammatory activation of human primary FLS isolated from RA patients and normal control subjects, and the underlying intracellular signaling molecules were also studied. We found that the plasma concentration of IL-27 in RA patients (n=112) was significantly higher than that in control subjects (n=46). Both normal and RA-FLS constitutively express functional IL-27 receptor heterodimer, gp130 and WSX-1, with more potent IL-27-mediated activation of signal transducers and activators of transcription (STAT)1 in RA-FLS. IL-27 was found to induce significantly higher cell surface expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 and release of inflammatory cytokine IL-6, chemokine CCL2, CXCL9, CXCL10 and matrix metalloproteinase (MMP)-1 of RA-FLS than that of normal FLS (all p < 0.05). The above findings therefore provide a new insight into the IL-27-activated immunopathological mechanisms mediated by distinct intracellular signal transductions in joint inflammation of RA and may have important therapeutic implications. / In the present study, we have investigated the mechanisms of the activation of human fibroblast-like synoviocytes (FLS) induced by various stimuli including interleukin (IL)-27, tumor necrosis factor (TNF)-alpha and IL-beta. The activation of human FLS was studied in terms of the release of cytokines and chemokines and the expression of adhesion molecules. / We investigated the in vitro effects of uric acid crystals, alone or in combination with inflammatory cytokine TNF-alpha or IL-beta on the pro-inflammatory activation of human FLS from RA patients and normal control subjects, and the underlying intracellular signaling molecules were also determined. In the present study, uric acid crystals were found to result in a significant increase of inflammatory cytokine IL-6, chemokine CXCL8 and MMP-1 from both normal and RA-FLS (all p < 0.05). Moreover, additive or synergistic effect was observed in the combined treatment of uric acid crystals and TNF-alpha or IL-1beta on the release of IL-6, CXCL8 and MMP-1 from both normal and RA-FLS. Further investigations showed that the release of inflammatory cytokine, chemokine and matrix metalloproteinase stimulated by uric acid crystals was differentially regulated by intracellular activation of extracellular signal-regulated kinase (ERK) and JNK pathways. Our results therefore provide a new insight into the endogenous danger signal uric acid crystals-activated immunopathological mechanisms mediated by distinct intracellular signal transductions in joint inflammation, and also provide biochemical basis for the development of new modality for inflammatory rheumatic diseases. / Chen, Dapeng. / Adviser: Wong Chun Kwok. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 203-240). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Wong, Chi Bun. / Thesis submitted in: Nov 2006. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 116-127). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / 摘要 --- p.v / Abbreviations --- p.vii / List of Table and Figures --- p.ix / Table of Contents --- p.x / Chapter Chapter 1 --- p.1 / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Identification of the proteins regulated by BRE when BRE was over-expressed or silencedin C2C12 and D122 --- p.1 / Chapter 1.1.1 --- What is BRE? --- p.1 / Chapter 1.1.2 --- BRE gene is Highly Conserved --- p.2 / Chapter 1.1.3 --- BRE binds to the Intracellular Domain of TNFR1 and Fas --- p.3 / Chapter 1.1.4 --- BRE Suppresses Apoptosis --- p.4 / Chapter 1.1.5 --- "BRE forms a Holoenzyme Complex with BRCA1, BARD1 and BRCC36" --- p.4 / Chapter 1.16 --- Roles of the Differentially Expressed Proteins Identified in the siRNA knockdown Experiments --- p.5 / Chapter 1.1.6.1 --- Akt3 --- p.5 / Chapter 1.1.6.2 --- Mdm2/4 --- p.6 / Chapter 1.1.6.3 --- Prohibitin --- p.7 / Chapter 1.1.6.4 --- Carbonic Anhydrase III --- p.8 / Chapter 1.1.6.5 --- 26S Proteasome --- p.8 / Chapter 1.2 --- The Role of BRE in Liver: a morphological approach --- p.9 / Chapter 1.2.1 --- The General Structure of the Liver. --- p.9 / Chapter 1.2.2 --- The Essential Functions of the Liver --- p.11 / Chapter 1.2.3 --- Inflammation of the Liver --- p.11 / Chapter 1.2.3.1 --- Hepatitis --- p.11 / Chapter 1.2.3.2 --- Acute Hepatitis --- p.12 / Chapter 1.2.3.3 --- Chronic Hepatitis --- p.12 / Chapter 1.2.4 --- Necrosis and Apoptosis --- p.13 / Chapter 1.2.5 --- The Apoptotic Pathway --- p.14 / Chapter 1.2.6 --- Hepatic Necrosis is Divided into Different Zones --- p.16 / Chapter 1.2.6.1 --- Hepatitis Necrosis is Categorized into 3 Zones --- p.16 / Chapter 1.2.7 --- Carbon Tetrachloride (CCL4) --- p.16 / Chapter 1.2.8 --- TNFa is a Pleiotropic Cytokine --- p.17 / Chapter 1.3 --- The Objectives of This Project --- p.20 / Chapter Chapter 2 --- p.21 / Chapter 2. --- Materials and Methods --- p.21 / Chapter 2.1 --- Animals --- p.21 / Chapter 2.2 --- Adminstration of Carbon Tetrachloride and Corn Oil --- p.21 / Chapter 2.3 --- Cell Cultures --- p.22 / Chapter 2.4 --- Cell Culturing --- p.22 / Chapter 2.5 --- Gene Silencing with Small Interfering RNA (siRNA) --- p.23 / Chapter 2.5.1 --- Transfection with BRE siRNA --- p.24 / Chapter 2.6 --- Cell Proliferation Assays --- p.24 / Chapter 2.7 --- In-Situ Hybridization of BRE Sense and Antisense Probes --- p.25 / Chapter 2.8 --- Immunohistological Staining --- p.26 / Chapter 2.9 --- Semi-Quantitative RT-PCR --- p.28 / Chapter 2.10 --- Comparative Proteomics --- p.29 / Chapter 2.10.1 --- Sample Preparation for Two Dimensional Gel Electrophoresis --- p.29 / Chapter 2.10.2 --- Two Dimensional Polyacrylamide Gel Electrophoresis --- p.30 / Chapter 2.10.3 --- In-Gel Digestion and MALDI-TOF Analysis --- p.31 / Chapter 2.11 --- Western Blotting --- p.32 / Chapter 2.12 --- Flow Cytometry --- p.34 / Chapter 2.13 --- Haematoxylin and Eosin Staining (H&E) --- p.34 / Chapter Chapter 3 --- p.36 / Chapter 3. --- Results --- p.36 / Chapter 3.1 --- BRE expression in C2C12 cells --- p.36 / Chapter 3.2 --- Comparative Proteomic Profile of BRE silenced C2C12 cells --- p.41 / Chapter 3.3 --- Effect of Silencing BRE on C2C12 cell Proliferation --- p.49 / Chapter 3.4 --- Effects of BRE over-expression in D122 cells --- p.54 / Chapter 3.5 --- BRE Expression in the Liver --- p.62 / Chapter 3.5.1 --- Histological Analysis of Liver Sections after 24 hours of CCL4 Insult --- p.62 / Chapter 3.5.2 --- BRE Expression in the Liver --- p.62 / Chapter 3.6 --- Histological Study of Liver Treated with CCL4 --- p.67 / Chapter 3.7 --- BRE Expression in Experimental Liver --- p.76 / Chapter Chapter 4 --- p.92 / Chapter 4. --- Discussion --- p.92 / Chapter 4.1 --- Expression of BRE in C2C12 --- p.92 / Chapter 4.2 --- The Regulatory Function of BRE --- p.96 / Chapter 4.3 --- The Relationship Between BRE and p53 --- p.98 / Chapter 4.4 --- The Relationship Between BRE and NFkB --- p.104 / Chapter 4.5 --- BRE Expression in Normal Control and CCL4 Treated Livers --- p.105 / Chapter 4.6 --- A Possible Explanation for the Necrosis Pattern Observed --- p.107 / Chapter 4.7 --- The Relationship Between BRE and the TNF Receptors --- p.109 / Chapter Chapter 5 --- p.112 / Chapter 5. --- Conclusion and Future Prospects --- p.112 / References --- p.116

Li Qing. / "July 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 161-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Airway bronchial epithelial cells play important roles in host defense, inflammation and regulation of immune responses. Activated bronchial epithelial cells are potent sources of a wide variety of soluble and cell-surface molecules that can alter the biological functions of inflammatory cells in the airways. Molecular mechanisms regulating the production of inflammatory mediators from bronchial epithelial cells remain to be fully elucidated. / All of the above findings suggest that human bronchial epithelial cells could be activated by a variety of stimuli in airway inflammatory reactions. Besides, different intracellular signaling pathways could regulate the activation of human bronchial epithelial cells in response to different stimuli. Our results therefore provide new insight into the molecular mechanisms involved in airway inflammatory diseases and may have important therapeutic implications. / Basophils are the accessory cell type required for T helper (Th)2 induction and initiators in IgE-mediated chronic allergic inflammation in response to allergens. Number of basophils and Th17 cells increases at the sites of allergic inflammation in the airways of allergic asthmatic patients. To elucidate the interaction among the activation of human bronchial epithelial cells, Th17 cells, and basophils, we investigated the activation effects of Th17 hallmark cytokine IL-17A on the human primary bronchial epithelial cells/BEAS-2B bronchial epithelial cells and human primary basophils/ KU812 basophilic cells. Human bronchial epithelial cells and basophils were cultured either together or separately in the presence or absence of IL-17A stimulation. Co-culture of human bronchial epithelial cells and basophils could significantly increase the release of inflammatory cytokine IL-6 and mononuclear chemoattractant protein-1 (MCP-1/CCL2), a chemokine for basophils, eosinophils and monocytes, while human bronchial epithelial cells were the main source for releasing IL-6 and CCL2. Such induction was synergistically enhanced upon the activation of IL-17A. The use of transwell inserts in the co-culture system demonstrated that the direct interaction between these two cell types was necessary for IL-6 and CCL2 release induced by IL-17A. Surface expression of intercellular adhesion molecule-1 (ICAM-1) on the human bronchial epithelial cells was also up-regulated upon their interaction. The interaction of human bronchial epithelial cells and basophils under IL-17A stimulation was differentially regulated by extracellular signal-regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK), p38 mitogen activated protein kinase (MAPK) and nuclear factor (NF)-kappaB pathways. Our findings therefore suggest a novel immunopathological role of human Th17 cells and basophils in allergic asthma through the activation of granulocytes-mediated inflammation initiated by the direct interaction between human basophils and bronchial epithelial cells. / IL-27 is a novel member of the IL-6/IL-12 family cytokines that are produced early by antigen-presenting cells (APCs) during immune responses. IL-27 can drive the commitment of naive T cells to a Th1 phenotype and inhibit inflammation in later phases of infection. Recent evidence has suggested that human bronchial epithelial cells with the expression of IL-27 receptor complex are potential target cells of IL-27. Here we investigated the in vitro effects of IL-27, alone or in combination with inflammatory cytokine TNF-alpha on the pro-inflammatory activation of human bronchial epithelial cells, and the underlying intracellular signaling molecules were also studied. IL-27 was found to up-regulate ICAM-1 expression on the surface of human bronchial epithelial cells, and a synergistic effect was observed in the combined treatment of IL-27 and TNF-alpha on the surface expression of ICAM-1. Although IL-27 did not alter the basal IL-6 secretion from human bronchial epithelial cells, it could significantly enhance TNF-alpha-induced IL-6 production. The synergistic effects on the induction of ICAM-1 and IL-6 were partially due to the up-regulated expression of TNF-alpha receptor (p55TNFR) on the surface of human bronchial epithelial cells induced by IL-27. Further investigations showed that the enhanced production of ICAM-1 and IL-6 in human bronchial epithelial cells activated by IL-27 and TNF-alpha was differentially regulated by phosphatidylinositol 3-OH kinase (PI3K)-Akt, p38 MAPK and NF-kappaB pathways. Our study therefore suggests a potential role of IL-27 and TNF-alpha in the pathogenesis of airway infection or inflammatory diseases. / In the present study, we investigated the mechanisms of the activation of human bronchial epithelial cells induced by various stimuli including interleukin (IL)-17A, IL-27, tumor necrosis factor (TNF)-alpha and human basophils. The activation of human bronchial epithelial cells was studied in terms of the expression of cytokines, chemokines and adhesion molecules. Using intracellular staining with flow cytometry and selective pharmacological inhibitors, we further investigated the underlying intracellular signaling mechanisms regulating the activation of human bronchial epithelial cells. / Cao, Ju. / Advisers: Chun K. Wong; Christopher W. K. Lam. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 175-202). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

L’interleukine (IL)-17 et le TNFa sont deux cytokines pro-inflammatoires jouant un rôle important dans diverses maladies inflammatoires systémiques et auto-immunes affectant différents organes et tissus comme le foie et les muscles. Cependant, les rôles de l’IL-17 et du TNFa restent encore mal compris dans les muscles et le foie, qui est impliqué dans la réponse en phase aiguë. En utilisant des cultures de myoblastes, d’hépatocytes et de cellules stellaires hépatiques humaines, nous avons trouvé que l’IL-17 et le TNFa augmentent en synergie la sécrétion de la cytokine pro-inflammatoire IL-6 et de plusieurs chimiokines. Dans les myoblastes, l’IL-17 et le TNFa induisent un stress oxydatif et une dérégulation de calcium montrant ainsi que les processus pathologiques immuns et non-immuns interagissent. Dans les hépatocytes, en augmentant en synergie les niveaux de la CRP et des transaminases, l’IL-17 et le TNFa participent à l’inflammation systémique et aux dommages cellulaires. Etant donné que des infiltrats de cellules immunitaires sont retrouvés lors d’atteintes inflammatoires, les interactions cellulaires contribuent certainement à la chronicité de l’inflammation. Des cellules mononuclées du sang périphérique activées ou non ont ainsi été placées en co-cultures avec les myoblastes, les hépatocytes et les cellules stellaires. Par comparaison aux monocultures, les productions de l’IL-6 et de la chimiokine IL-8 étaient augmentées dans les co-cultures. L’IL-17 et le TNFa contribuaient partiellement à ces effets. Les effets systémiques de l’IL-17 et du TNFa en font donc des cibles thérapeutiques attrayantes pour le traitement des nombreuses maladies inflammatoires systémiques / Interleukin-17A (IL-17) and tumor necrosis factor-a (TNFa) are two pro-inflammatory cytokines playing an important role in various systemic inflammatory and autoimmune disorders affecting different organs and tissues including the liver and the muscles. However, the roles of IL-17 and TNFa are not fully understood in the muscles and also in liver, which is crucial in the acute phase response. By using cultures of human myoblasts, primary human hepatocytes, human HepaRG cells and LX-2 hepatic stellate cells, we found that IL-17 and TNFa increase in synergy the production of the pro-inflammatory cytokine IL-6 and chemokines (IL-8, CCL20, MCP-1). In myoblasts, the IL-17 and TNFa stimulation induces endoplasmic reticulum stress and calcium dysregulation showing that immune and non-immune pathogenic mechanisms interplay. In hepatocytes, IL-17 and TNFa mediate systemic inflammation and cell damage by increasing in synergy the CRP acute-phase protein and transaminase levels through the induction of IL-6. Since active liver and muscle disorders are characterized by inflammatory infiltrates of immune cells, the cell interactions play certainly an important role in the chronicity of the inflammation. Peripheral blood mononuclear cells activated or not were therefore co-cultured with myoblasts, hepatocytes and/or hepatic stellate cells to assess the inflammatory role of the cell-cell interactions. Co-cultures enhance the production of IL-6 and IL-8 compared to monocultures. IL-17 and TNFa contribute partially to these inductions. The systemic effects of IL-17 and/or TNFa make them attractive therapeutic targets for the treatment of various systemic inflammatory disorders

Thesis (Ph.D. in Immunology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 144-178). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;