Expression of Toll-like Receptor 9 in nose, peripheral blood and bone marrow during symptomatic allergic rhinitis

Fransson, Mattias; Benson, Mikael; Erjefält, Jonas; Jansson, Linda; Uddman, Rolf; Björnsson, Sven; Cardell, Lars Olaf; Adner, Mikael

doi:10.1186/1465-9921-8-17

Cited by 53 publications

(50 citation statements)

References 41 publications

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“…TLR9 is strongly expressed in normal nasal epithelium, and its expression is significantly downregulated in the SNEC of patients with CRSwNP. 15,16 In addition, activation of TLR9 by CpG is known to be Th1 polarizing and capable of suppressing Th2 inflammation. Given that CRSwNP is a Th2-biased eosinophilic inflammatory condition characterized by bacterial colonization, these features of TLR9 biology suggest a possible role in CRSwNP pathogenesis.…”

mentioning

confidence: 99%

Th2 Cytokines associated with Chronic Rhinosinusitis with Polyps Down-Regulate the Antimicrobial Immune Function of Human Sinonasal Epithelial Cells

Ramanathan

Lee

Spannhake

et al. 2008

American Journal of Rhinology

104

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Background-Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a disorder characterized by persistent eosinophilic Th2 inflammation and frequent sinonasal microbial colonization. It has been postulated that an abnormal mucosal immune response underlies disease pathogenesis. The relationship between Th2 inflammatory cytokines and the innate immune function of sinonasal epithelial cells (SNECs) has not been explored.

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mentioning

confidence: 99%

Th2 Cytokines associated with Chronic Rhinosinusitis with Polyps Down-Regulate the Antimicrobial Immune Function of Human Sinonasal Epithelial Cells

Ramanathan

Lee

Spannhake

et al. 2008

American Journal of Rhinology

104

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“…Cell morphology was determined by trypan blue staining and microscopy, and the total number of cells/ml was counted in a Bürker chamber. Flow cytometry on NAL has previously demonstrated an abundance of neutrophils among the leukocytes in NAL [22]. The composition of leukocytes in NAL consists of an average of 96% neutrophils, approximately 1% eosinophils and a few percent mononuclear cells.…”

Section: Methodsmentioning

confidence: 99%

Nasal Challenge with LPS Stimulates the Release of Macrophage Inflammatory Protein 1α

Ekman

Fransson

Rydberg

et al. 2009

Int Arch Allergy Immunol

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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 1α (MIP-1α) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1α 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-1α levels analyzed and expression of MIP-1α mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP-1α release, cell survival, and the involved signal pathways, were investigated. Results: LPS challenge caused an increase of MIP-1α 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-1α, which was reduced by inhibitors of transcription and of nuclear factor (NF)-κB, protein kinase C (PKC) and p38 MAPK pathways. Conclusions: Nasal LPS challenge results in release of MIP-1α. The release most likely originates from recruited neutrophils, via NF-κB-, PKC- and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apoptosis. MIP-1α may constitute an important mediator in neutrophilic airway disease.

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“…Results have shown TLR9 expression in several different cell types; the expression was generally higher in BM, and the onset of allergic rhinitis did not affect TLR9 expression [8]. Activated expression of TLR2 and TLR4 was also found in leukocytes from BM and PB during symptomatic allergic rhinitis [unpubl.…”

Section: Introductionmentioning

confidence: 99%

“…The TLR family comprises 10 different members in humans (TLR1–TLR10), each recognizing a conserved microbial structure and thereby initiating a host defense response [4, 5]. The virus-recognizing TLRs are TLR3, TLR7/8 and TLR9, which respond to viral double-stranded RNA , single-stranded RNA and CpG-DNA, respectively [5,6,7,8]. …”

Section: Introductionmentioning

confidence: 99%

TLR3 in Human Eosinophils: Functional Effects and Decreased Expression during Allergic Rhinitis

Månsson

Fransson

Adner

et al. 2009

Int Arch Allergy Immunol

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Background/Aim: Viral respiratory infections are increasingly implicated in allergic exacerbations. Virus-induced activation of eosinophils through Toll-like receptors (TLRs) could be involved. The present study was designed to examine TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB) during symptomatic allergic rhinitis, and to evaluate the functional responsiveness of TLR3 in purified eosinophils. Methods: BM and PB samples were obtained from healthy volunteers and patients with seasonal allergic rhinitis outside and during the pollen season. Eosinophils were analyzed for TLR3 expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an agonist for TLR3, was used to assess its functional role in purified eosinophils and the intracellular signaling pathways involved. Results: TLR3 expression was demonstrated in BM and PB eosinophils. It was higher in BM-derived than in circulating cells and it was downregulated in both compartments during symptomatic allergic rhinitis. TLR3 expression was also downregulated in the presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects mediated via the p38 mitogen-activated protein kinases and nuclear factor-ĸB signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)-induced IL-8 release. Conclusions: Eosinophils activated via TLR3 might be more able to home and recruit leukocytes to sites of inflammation. The decreased TLR3 expression during symptomatic allergic rhinitis and in the presence of Th2 cytokines indicates a role in allergic airway inflammation. Thus, eosinophils might function as a link between viral infections and exacerbations of allergic disease.

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Expression of Toll-like Receptor 9 in nose, peripheral blood and bone marrow during symptomatic allergic rhinitis

Cited by 53 publications

References 41 publications

Th2 Cytokines associated with Chronic Rhinosinusitis with Polyps Down-Regulate the Antimicrobial Immune Function of Human Sinonasal Epithelial Cells

Th2 Cytokines associated with Chronic Rhinosinusitis with Polyps Down-Regulate the Antimicrobial Immune Function of Human Sinonasal Epithelial Cells

Nasal Challenge with LPS Stimulates the Release of Macrophage Inflammatory Protein 1α

TLR3 in Human Eosinophils: Functional Effects and Decreased Expression during Allergic Rhinitis

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