| 61. |
- Che, Karlhans F., et al.
(författare)
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Complex Involvement of Interleukin-26 in Bacterial Lung Infection
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects.
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| 62. |
- Drakskog, Cecilia, et al.
(författare)
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Extensive qPCR analysis reveals altered gene expression in middle ear mucosa from cholesteatoma patients
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- The middle ear is a small and hard to reach compartment, limiting the amount of tissue that can be extracted and the possibilities for studying the molecular mechanisms behind diseases like cholesteatoma. In this paper 14 reference gene candidates were evaluated in the middle ear mucosa of cholesteatoma patients and two different control tissues. ACTB and GAPDH were shown to be the optimal genes for the normalisation of target gene expression when investigating middle ear mucosa in multiplex qPCR analysis. Validation of reference genes using c-MYC expression confirmed the suitability of ACTB and GAPDH as reference genes and showed an upregulation of c-MYC in middle ear mucosa during cholesteatoma. The occurrence of participants of the innate immunity, TLR2 and TLR4, were analysed in order to compare healthy middle ear mucosa to cholesteatoma. Analysis of TLR2 and TLR4 showed variable results depending on control tissue used, highlighting the importance of selecting relevant control tissue when investigating causes for disease. It is our belief that a consensus regarding reference genes and control tissue will contribute to the comparability and reproducibility of studies within the field.
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| 63. |
- Ekman, Anna-Karin, et al.
(författare)
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Allergen-Induced Accumulation of CD68(-), CD123(+) Dendritic Cells in the Nasal Mucosa
- 2011
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 155:3, s. 234-242
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dendritic cells are antigen-presenting cells central to the immune system. They activate and orchestrate the innate and the adaptive immune systems. This phenotypically diverse group can be further divided into 2 subsets, the CD11c(+) myeloid dendritic cells (mDCs) and the CD123(+) plasmacytoid dendritic cells (pDCs). The aim of the study was to investigate the effect of allergen exposure on dendritic cells in subjects with allergic rhinitis. Methods: Atopic and non-atopic subjects were challenged intranasally with birch or timothy allergen. Nasal biopsies were taken before and 24 h after challenge, and were, after CD68 exclusion, stained for expression of CD11c and CD123 to identify dendritic cell subsets. The effect of allergic mediators on CD68(-), CD123(+) cells was studied with flow cytometry analysis in peripheral blood. Results: The amount of CD68(-), CD123(+) cells increased in the nasal sub-epithelium upon allergen challenge, whereas the number of CD68(-), CD11c(+) cells was unaffected. In vitro study of the effect of inflammatory mediators on pDC phenotype showed an increased activation in response TNF-alpha, IL-4 and CpG. Furthermore, TNF-alpha caused a higher activation among atopic than non-atopic subjects. Conclusions: An increased number of CD68(-), CD123(+) dendritic cells along with the positive pDC response following stimulation with inflammatory mediators suggest that the increased pDCs may be of an activated phenotype. It also suggests that the inflammatory response by pDCs to mediators such as TNF-alpha may be markedly higher in atopic subjects. These data support the notion of pDCs as important participants in allergic rhinitis. Copyright (C) 2011 S. Karger AG, Basel
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| 64. |
- Ekman, Anna-Karin, et al.
(författare)
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Nasal Challenge with LPS Stimulates the Release of Macrophage Inflammatory Protein 1 alpha
- 2009
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 149:2, s. 154-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1 alpha in LPS-induced nasal inflammation. Methods: Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1 alpha levels analyzed and expression of MIP-1 alpha mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP1 alpha release, cell survival, and the involved signal pathways, were investigated. Results: LPS challenge caused an increase of MIP-1 alpha in nasal lavage. No corresponding change in mRNA expression was seen in nasal biopsies, suggesting the increase was not due to epithelial synthesis. Neutrophil numbers increased after LPS provocation. Treatment of isolated neutrophils with LPS delayed neutrophil apoptosis and resulted in a time-and concentration-dependent release of MIP-1 alpha, which was reduced by inhibitors of transcription and of nuclear factor (NF)-kappa B, protein kinase C (PKC) and p38 MAPK pathways. Conclusions: Nasal LPS challenge results in release of MIP-1 alpha. The release most likely originates from recruited neutrophils, via NF-kappa B-, PKC-and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apop tosis. MIP-1 alpha may constitute an important mediator in neutrophilic airway disease. Copyright (C) 2009 S. Karger AG, Basel
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| 65. |
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| 66. |
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| 67. |
- Fransson, Mattias, et al.
(författare)
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A role for neutrophils in intermittent allergic rhinitis
- 2004
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Ingår i: Acta Otolaryngol. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 124:5, s. 616-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In patients with intermittent allergic rhinitis, allergen challenge may induce both early- and late-phase responses. The aim of this study was to examine the correlation between inflammatory cells in the nasal lavage fluid and clinical parameters following pollen challenge. MATERIAL AND METHODS: Nasal lavage fluids were obtained from 29 patients with intermittent allergic rhinitis before and 1 and 6 h after allergen provocation, representing the control, early and late phases, respectively. Symptom and rhinoscopic scores were registered on the same occasions. Inflammatory cells were determined in the nasal fluid. RESULTS: The early phase was characterized by increased symptom scores, rhinoscopic signs of oedema and secretion and neutrophilia. In the late phase, symptom scores had diminished, but the signs of ongoing secretion remained. Both the total nasal symptom score and the secretion score correlated with the number of neutrophils in lavage fluids at 1 h. The eosinophil count did not increase during the early or late phases. CONCLUSION: A single allergen provocation induces an early-phase response dominated by neutrophils, with secretion being the only clinical sign remaining during the late phase. The increase in neutrophil numbers correlated with the registration of secretory symptoms. The presented data indicate a role for neutrophils in intermittent allergic rhinitis and their relation with secretory parameters makes it intriguing to speculate that neutrophils may function as promoters of nasal secretion.
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| 68. |
- Fransson, Mattias, et al.
(författare)
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Expression of Toll-like receptor 9 in nose, peripheral blood and bone marrow during symptomatic allergic rhinitis.
- 2007
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Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X .- 1465-9921. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Allergic rhinitis is an inflammatory disease of the upper airway mucosa that also affects leukocytes in bone marrow and peripheral blood. Toll-like receptor 9 (TLR9) is a receptor for unmethylated CpG dinucleotides found in bacterial and viral DNA. The present study was designed to examine the expression of TLR9 in the nasal mucosa and in leukocytes derived from different cellular compartments during symptomatic allergic rhinitis. METHODS: The study was based on 32 patients with seasonal allergic rhinitis and 18 healthy subjects, serving as controls. Nasal biopsies were obtained before and after allergen challenge. Bone marrow, peripheral blood and nasal lavage fluid were sampled outside and during pollen season. The expression of TLR9 in tissues and cells was analyzed using immunohistochemistry and flow cytometry, respectively. RESULTS: TLR9 was found in several cell types in the nasal mucosa and in different leukocyte subpopulations derived from bone marrow, peripheral blood and nasal lavage fluid. The leukocyte expression was generally higher in bone marrow than in peripheral blood, and not affected by symptomatic allergic rhinitis. CONCLUSION: The widespread expression of TLR9 in the nasal mucosa along with its rich representation in leukocytes in different compartments, demonstrate the possibility for cells involved in allergic airway inflammation to directly interact with bacterial and viral DNA.
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| 69. |
- Fransson, Mattias, et al.
(författare)
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Lipopolysaccharide-induced down-regulation of uteroglobin in the human nose.
- 2007
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 127:3, s. 285-291
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion. Lipopolysaccharide (LPS) challenge of the human nose has the capacity to reduce the amount of natural anti-inflammatory proteins, such as uteroglobin. Objectives. Nasal challenge with LPS, an activator of innate immunity, has been shown to increase the amount of pro-inflammatory mediators in nasal lavage fluid. Uteroglobin is a newly described anti-inflammatory mediator that is secreted in the nose. This study examined the effect of nasal LPS application on the level of uteroglobin in nasal lavage fluid as well as on the expression of uteroglobin in nasal mucosa. Materials and methods. Thirty-eight volunteers were challenged nasally with either 50 mu g LPS or vehicle; 6 h later, nasal lavage fluid was collected and a nasal biopsy was obtained. Levels of uteroglobin, albumin and the pro-inflammatory mediators interleukin (IL)-6 and IL-8 were analysed in the lavage fluids using enzyme-linked immunosorbent assays (ELISAs). Biopsies were used for either quantification of uteroglobin mRNA by real-time PCR or for localization of the corresponding protein with immunohistochemistry. Results. The uteroglobin level decreased in nasal lavage fluid following LPS challenge, whereas the levels of IL-6 and albumin increased. Uteroglobin was mainly seen in the respiratory epithelium and its mRNA expression decreased as a consequence of the LPS challenge.
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| 70. |
- Fransson, Mattias, et al.
(författare)
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Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis
- 2005
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 6:100
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen. METHODS: 27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors 2, 3 and 4 with real-time polymerase chain reaction, whereas specimens achieved in conjunction with allergen challenge were used for immunohistochemical localization and quantification of corresponding proteins. RESULTS: mRNA and protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all specimens. An increase in protein expression for all three receptors could be seen following allergen challenge, whereas a significant increase of mRNA only could be obtained for Toll-like receptor 3 during pollen season. CONCLUSION: The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation.
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