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Nasal Epithelium (nasal + epithelium)
Selected AbstractsMast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Masanori Miyata Abstract Epithelial cell-derived thymic stromal lymphopoietin (TSLP) is a master switch for asthma or atopic dermatitis by inducing a dendritic cell-mediated Th2-type allergic inflammation. Allergic rhinitis is also pathologically characterized by Th2-type allergic inflammation. This study demonstrates that mast cells regulate the epithelial TSLP expression in allergic rhinitis. TSLP expression was found to be up-regulated predominantly in the nasal epithelium in the ovalbumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis, which was abolished in mast cell-deficient WBB6F1-W/Wv in comparison with control WBB6F1-+/+ mice. Similarly, the epithelial TSLP expression was reduced in Fc receptor , chain (Fc,R)-deficient mice, where the high-affinity IgE receptor (Fc,RI) is not expressed on mast cells, in comparison with control C57BL/6 mice. Furthermore, the administration of neutralizing TSLP antibody during the challenge phase of OVA inhibited the development of allergic rhinitis. These results suggest that the direct stimulation of epithelial cells by antigens alone may not be sufficient to induce TSLP expression in the nasal epithelium, and that mast cell regulation of epithelial TSLP expression, possibly via Fc,RI, plays an important role in the development of allergic rhinitis. [source] Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1-2 2010David Mitchell Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6,4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirwayÔ) and human skin (EpiDermÔ) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. [source] The biopharmaceutical aspects of nasal mucoadhesive drug deliveryJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2001Michael Ikechukwu Ugwoke Nasal drug administration has frequently been proposed as the most feasible alternative to parenteral injections. This is due to the high permeability of the nasal epithelium, allowing a higher molecular mass cut-off at approximately 1000 Da, and the rapid drug absorption rate with plasma drug profiles sometimes almost identical to those from intravenous injections. Despite the potential of nasal drug delivery, it has a number of limitations. In this review, the anatomy and physiology of the nasal cavity, as well as ciliary beating and mucociliary clearance as they relate to nasal drug absorption, are introduced. The rationale for nasal drug delivery and its limitations, some factors that influence nasal drug absorption, and the experimental models used in nasal drug delivery research are also reviewed. Nasal mucoadhesion as a promising method of nasal absorption enhancement is discussed, and factors that influence mucoadhesion, as well as safety of nasal mucoadhesive drug delivery systems are reviewed in detail. Nasal drug administration is presently mostly used for local therapies within the nasal cavity. Anti-allergic drugs and nasal decongestants are the most common examples. However, nasal drug administration for systemic effects has been practised since ancient times. Nasally-administered psychotropic drugs by native Americans, the use of tobacco snuffs, and nasal administration of illicit drugs such as cocaine are all well known (Illum & Davis 1992). Nowadays, the nasal cavity is being actively explored for systemic administration of other therapeutic agents, particularly peptides and proteins (Illum 1992; Edman & Bjork 1992), as well as for immunization purposes (Lemoine et al 1998). To better understand the basis for nasal drug absorption and factors that can influence it, a brief review of the anatomy and physiology of the nose is appropriate. [source] Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?ALLERGY, Issue 10 2010J. Bogefors To cite this article: Bogefors J, Rydberg C, Uddman R, Fransson M, Månsson A, Benson M, Adner M, Cardell LO. Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis? Allergy 2010; 65: 1222,1226. Abstract Background:, Recently, a new set of pattern-recognition receptors, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. The knowledge about NLRs in human airways is limited. Aim of the study:, To investigate presence of NLRs in the human nose of healthy individuals and patients with intermittent allergic rhinitis outside and during pollen season. Methods:, The expression of Nod1, Nod2, and Nalp3 in nasal biopsies was determined with real-time RT-PCR and immunohistochemistry. Cultured primary human nasal epithelial cells (HNECs) were analyzed using real-time RT-PCR and flow cytometry to further verify the presence of NLRs in the epithelium. Results:, Immunohistochemical analysis revealed presence of Nod1, Nod2, and Nalp3 in the nasal epithelium. This was corroborated in cultured HNECs. Patients suffering from symptomatic allergic rhinitis exhibited lower Nod1 and Nalp3 mRNA levels than both controls and patients during pollen season. Nod2 expression was found in all specimens tested, but no differences were seen between the three groups. Conclusion:, Nod1, Nod2, and Nalp3 receptors were found to be present in the human nose. The expression of Nod1 and Nalp3 were down-regulated during pollen season among patients with allergic rhinitis. This opens up for new insights and novel therapeutic strategies in inflammatory airway disease. [source] Transcriptome dissection of gastric cancer: Identification of novel diagnostic and therapeutic targets from pathology specimensPATHOLOGY INTERNATIONAL, Issue 3 2009Wataru Yasui Gastric cancer is the fourth most common malignancy in the world, and mortality due to gastric cancer is second only to that from lung cancer. ,Transcriptome dissection' is a detailed analysis of the entire expressed transcripts from a cancer, for the purpose of understanding the precise molecular mechanism of pathogenesis. Serial analysis of gene expression (SAGE) is a suitable technique for performing transcriptome dissection. Gastric cancers of different stages and histology were analyzed on SAGE, and one of the largest gastric cancer SAGE libraries in the world was created (GEO accession number GSE 545). Through SAGE, many candidate genes have been identified as potential diagnostic and therapeutic targets for the treatment of gastric cancer. Regenerating islet-derived family, member 4 (Reg IV) participated in 5-fluorouracil (5-FU) resistance and peritoneal metastasis, and its expression was associated with an intestinal phenotype of gastric cancer and with endocrine differentiation. GW112 expression correlated with advanced tumor stage. Measurement of Reg IV and GW112 levels in sera indicated a sensitivity of 57% for detection of cancer. SPC18 participated in tumor growth and invasion through transforming tumor growth factor-, upregulation. Palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) was a useful marker for gastric hepatoid adenocarcinoma. Expression of SOX9, HOXA10, CDH17, and loss of claudin-18 expression were associated with an intestinal phenotype of gastric cancer. Information obtained from transcriptome dissection greatly contributes to diagnosis and treatment of gastric cancer. [source] Cytology in the diagnosis of rhinosinusitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2007M. Gelardi Nasal cytology is a diagnostic tool currently used in rhinology, with the aim of assessing cell changes in the nasal epithelium exposed to irritant or inflammatory agents. Its rationale is based on the knowledge that nasal mucosa of healthy individuals is constituted by four cytotypes (ciliata, mucipara, striata, and basalis) and does not show other cells except, rarely, neutrophils and, very rarely, bacteria. In this view, the detection of a given cell type different from these is a sign of possible pathology. The advantage and the diffusion of nasal cytology were increased by a number of factors such as the easiness of performance, the non-invasiveness allowing repetition (which is often needed in the efficacy monitoring of medical or surgical treatment of nasal diseases), and the low cost. This makes nasal cytology particularly feasible for application in children. The cytological feature characterizing infectious inflammation is the presence of abundant bacteria, which may be found in extracellular tissue and also inside neutrophils as a result of phagocytosis. In such clinical condition it is important to monitor the disease with cytological controls to verify the significant decrease, or the disappearance of inflammatory cells, which indicates the resolution of the pathology. [source] Bone marrow stem cells do not repopulate the healthy upper respiratory tract,PEDIATRIC PULMONOLOGY, Issue 4 2002Jane C. Davies MD Abstract Recent studies reported differentiation of both bone marrow and tissue-specific stem cells into cells of other organs. The demonstration that bone marrow stem cells differentiate into human hepatocytes in vivo has raised the possibility of new therapeutic approaches for liver disease. For diseases such as cystic fibrosis (CF), correction of the respiratory epithelium is being attempted by gene therapy. Differentiation of bone marrow stem cells into epithelium of the lung and airway was recently reported in an animal model, and would provide an alternative approach. We examined the nasal epithelium of female patients up to 15 years after gender-mismatched bone marrow transplantation. Donor-derived epithelial cells were sought with a combination of Y-chromosome fluorescence in situ hybridization and anti-cytokeratin antibody. In nasal brushing samples from 6 transplant-recipients, a median of 2.5% (range, 0.7,18.1%) of nuclei was male and identified as being of donor-origin. However, a complete absence of staining with anti-cytokeratin antibodies confirmed that these were not epithelial cells, but were likely to be either intraepithelial lymphocytes or mesenchymal cells. Following whole bone marrow transplantation, bone marrow progenitor cells do not differentiate into respiratory epithelium of the healthy upper airway. The differences between this and other studies could relate to the cells transplanted, to differential rates of turnover, or to the requirement for specific triggers to stimulate migration and differentiation. In the absence of such conditions, whole bone marrow transplantation is unlikely to provide a route for correction of the CF airway. Pediatr Pulmonol. 2002; 34:251,256. © 2002 Wiley-Liss, Inc. [source] Culture of nasal epithelial cells using chitosan-based membranesTHE LARYNGOSCOPE, Issue 10 2009Tsung-Wei Huang MD Abstract Objectives/Hypothesis: The aim of this study was to evaluate whether chitosan-based membranes can be used as scaffolds for growth and differentiation of nasal epithelial cells (NECs). Our final goal was to establish a novel methodology for enhancing the regeneration of the respiratory system. Study Design: Prospective study. Methods: Human NECs were cultured on three various substrates, e.g., chitosan membranes, collagen, and chitosan-collagen membranes. Morphology of NECs was examined via light and electron microscopy, the area of ciliated cells was measured by confocal microscopy, and ciliary beat frequency was also evaluated. Expression of mucin genes was investigated with reverse-transcription polymerase chain reaction. Results: NECs were found to be successfully adhesive with collagen and chitosan-collagen membranes at day 3 after seeding, but not with chitosan membranes. The cilia area on collagen were 6.1% ± 1.2%, 8.4% ± 1.4%, and 12.5% ± 1.9% at days 7, 14, and 21 after confluence, respectively, compared with 5.1% ± 0.9%, 8.6% ± 1.6%, and 12.3% ± 2.1% in chitosan-collagen membranes, exhibited nonsignificant difference (P > .05). There were no significant differences in ciliary beat frequency between each group. The expression levels of mucin genes, namely, MUC5AC, MUC5B, and MUC2, in NECs on both collagen and chitosan-collagen membranes did not differ significantly (P > .05). Conclusions: A small amount collagen mixed with chitosan substrate may improve the biocompatibility and promote the mucociliary differentiation in NECs. It appears that chitosan-collagen membrane is a promising scaffold for culture of the nasal epithelium, which sets the stage for studying tissue regeneration in the respiratory system. Laryngoscope, 2009 [source] Serum squamous cell carcinoma antigen is a useful biologic marker in patients with inverted papillomas of the sinonasal tractCANCER, Issue 1 2002Ryuji Yasumatsu M.D. Abstract BACKGROUND Inverted papilloma (IP) is a frequent benign sinonasal tumor that is characterized histologically by squamous metaplasia, epithelial acanthosis, and hyperplasia of the nasal epithelium. Because of its high recurrence rate and malignant transformation potential, careful long-term follow up is necessary. METHODS The purpose of the current report was to study the expression of squamous cell carcinoma (SCC) antigen in sinonasal IPs and to evaluate the usefulness of SCC antigen as a biologic marker for the follow-up of patients with sinonasal IP. The expression of SCCA1 in three sinonasal IP cases, three sinonasal SCC cases, and cases of normal nasal epithelium were examined by Western blot analysis, and the SCCA1 expression pattern in 31 IP specimens and 4 carcinoma in IP specimens were evaluated immunohistochemically. The serum levels of SCC antigen in 11 patients with sinonasal IP also were analyzed. RESULTS SCCA1 was overexpressed in all three sinonasal IP tissues compared with sinonasal SCC tissues or normal nasal epithelium. SCCA1 cytoplasmic immunoreactivity was detected in the suprabasal epidermal keratinocytes of all 31 sinonasal IP cases. In the four carcinoma in IP specimens, SCCA1 expression in the papillomatous lesion was more intense than in the cancerous lesion. The serum SCC antigen level was high in 10 of 11 patients with IP (91%) and significantly decreased after surgical resection of the tumors. CONCLUSIONS The results of the current study indicate that SCCA1 frequently is overexpressed and may play a biologic role in the development of sinonasal IPs. Serum SCC antigen may be a useful biologic marker in patients with sinonasal IP. Cancer 2002;94:152,8. © 2002 American Cancer Society. [source] The novel use of the human nasal epithelial cell line RPMI 2650 as an in vitro model to study the influence of allergens and cytokines on transforming growth factor-, gene expression and protein releaseCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2005R. J. Salib Summary Background The epithelial accumulation of mast cells is a feature of allergic rhinitis and this has been linked to the expression of the known mast cell chemoattractant transforming growth factor-, (TGF-,) at this site. Little is known concerning the regulation of TGF-, gene expression or protein release by nasal epithelial cells. To address this we have utilized the RPMI 2650 human nasal epithelial cell line, which has some features that closely resemble normal nasal epithelium and has been reported to secrete a TGF-,-like molecule. Objectives To investigate the regulation of TGF-, gene expression and protein secretion in RPMI 2650 nasal epithelial cells following exposure to allergens (house dust mite (HDM) and grass pollen) and mast cell associated T-helper type 2 (Th2) cytokines (IL-4, IL-13, and TNF-,). Methods Light and scanning electron microscopy was used to evaluate the morphology of RPMI 2650 cells in culture, enzyme-linked immunosorbent assay was used to investigate their TGF-, secretory capacity and the identification of the TGF-, isotype(s) involved, flow cytometry was used to demonstrate the presence of TGF-, receptors on the RPMI 2650 cells, and the quantitative real-time TaqMan PCR was used to measure TGF-, gene expression. Results TGF-,2 was identified as the main isotype secreted by the RPMI 2650 cells. HDM allergens and TNF-, increased both TGF-, gene expression and protein release from these cells, whereas grass pollen, IL-4, and IL-13 were without effect. Conclusions The RPMI 2650 nasal epithelial cell line represents a valid in vitro model to evaluate the regulation of TGF-, biology. In this system HDM allergens have stimulatory activity that is fundamentally different from that of grass pollen allergens, and the Th2 cytokines IL-4 and IL-13 are without effect. The ability of TNF-, to up-regulate both TGF-, gene expression and protein release indicates that mast cell,epithelial interactions concerning TGF-, are bi-directional and this may be fundamental to epithelial immunoregulation. The availability of a model system, such as the RPMI 2650 cells, will enable the early evaluation of future novel and targeted interventions directed toward the aberrant responses of upper airway structural cells. [source] | ||||||||||