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.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Thesis (MScMedSc (Pharmacology))--University of Stellenbosch, 2005. / In this thesis, research results are reported on the role of natural and synthetic surfactants on the in vitro permeability characteristics of various chemical compounds across porcine (buccal, bronchial, arterial, venous and rectal) and human (vaginal) tissues. The permeability flux values of the different compounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone, vasopressin, oxytocin, zidovudine and isoniazid) were determined using a continuous flow-through diffusion system. Mean steady state flux values were compared statistically by means of a t-test at a significance level of 5% as well as an F-test using whole curve comparisons. The results indicated that the synthetic pulmonary surfactant Biopolsurf is an effective enhancer for the permeation of chemical compounds through most of the tissues tested and that molecular weight, electrostatic charge, partitioning of the molecules in surfactant and surfactant concentration play an important role in trans membrane diffusion. In addition the epithelial permeability of the different types of tissues for various chemical compounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone, vasopressin and oxytocin) across the above tissues were compared. The results obtained showed that the permeability flux values of the compounds across porcine bronchial and human vaginal tissues were consistently similar and that porcine buccal tissue had the lowest permeability of all tissues tested. This was in agreement with previous in vitro studies. It was concluded that a wide variation in the permeability characteristics of different epithelia exists and that the pulmonary epithelium, due to its high permeability, is probably the most effective epithelium for drug delivery purposes, especially for drugs that undergo extensive gastrointestinal or hepatic first-pass metabolism.

published_or_final_version / abstract / Molecular Biology / Master / Master of Philosophy

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Medicine / Master / Master of Philosophy

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy