dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant

Brandelius, Angelica; Yudina, Yulyana; Calvén, Jenny; Bjermer, Leif; Andersson, Morgan; Persson, C. G. A.; Uller, Lena

doi:10.1016/j.pupt.2010.10.004

Cited by 38 publications

(47 citation statements)

References 31 publications

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“…The transcription factor NFkB mediates cytokine gene activation downstream of TLR3 signaling. Drugs that inhibit NFkB by stabilizing its binding to IkB have also been shown to be effective inhibitors of TSLP generation in dsRNA-stimulated BEC from healthy and diseased donors [29] . Additionally, such drugs have produced a less desirable inhibition of the antiviral IFN-␤ in these BEC [Uller et al unpubl.…”

Section: Discussionmentioning

confidence: 99%

Viral Stimuli Trigger Exaggerated Thymic Stromal Lymphopoietin Expression by Chronic Obstructive Pulmonary Disease Epithelium: Role of Endosomal TLR3 and Cytosolic RIG-I-Like Helicases

Calvén¹,

Yudina²,

Hällgren

et al. 2011

J Innate Immun

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Background: Rhinovirus (RV)-induced chronic obstructive pulmonary disease (COPD) exacerbations exhibit TH₂-like inflammation. We hypothesized that RV-infected bronchial epithelial cells (BEC) overproduce TH₂-switching hub cytokine, thymic stromal lymphopoietin (TSLP) in COPD. Methods: Primary BEC from healthy (HBEC) and from COPD donors (COPD-BEC) were grown in 12-well plates, infected with RV16 (0.5–5 MOI) or stimulated with agonists for either toll-like receptor (TLR) 3 (dsRNA, 0.1–10 µg/ml) or RIG-I-like helicases (dsRNA-LyoVec, 0.1–10 µg/ml). Cytokine mRNA and protein were determined (RTqPCR; ELISA). Results: dsRNA dose-dependently evoked cytokine gene overproduction of TSLP, CXCL8 and TNF-α in COPD-BEC compared to HBEC. This was confirmed using RV16 infection. IFN-β induction did not differ between COPD-BEC and HBEC. Endosomal TLR3 inhibition by chloroquine dose-dependently inhibited dsRNA-induced TSLP generation and reduced generation of CXCL8, TNF-α, and IFN-β. Stimulation of cytosolic viral sensors (RIG-I-like helicases) with dsRNA-LyoVec increased production of CXCL8, TNF-α, and IFN-β, but not TSLP. Conclusions: Endosomal TLR3-stimulation, by dsRNA or RV16, induces overproduction of TSLP in COPD-BEC. dsRNA- and RV-induced overproduction of TNF-α and CXCL8 involves endosomal TLR3 and cytosolic RIG-I-like helicases and so does the generation of IFN-β in COPD-BEC. RV16 and dsRNA-induced epithelial TSLP may contribute to pathogenic effects at exacerbations and development of COPD.

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Section: Discussionmentioning

confidence: 99%

Viral Stimuli Trigger Exaggerated Thymic Stromal Lymphopoietin Expression by Chronic Obstructive Pulmonary Disease Epithelium: Role of Endosomal TLR3 and Cytosolic RIG-I-Like Helicases

Calvén¹,

Yudina²,

Hällgren

et al. 2011

J Innate Immun

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“…Genetic polymorphisms in the promoter region of TSLP and IL33R (IL1RL1) are associated with increased risk of asthma (Harada et al, 2011). Of note, airway ECs from asthmatic patients secrete more TSLP when exposed to dsRNA (viral analog) (Brandelius et al, 2011). This might partly explain why patients with asthma get an exacerbation of their disease after being exposed to such triggers (Jackson and Johnston, 2010).…”

Section: Alterations In Ec-repairing Factors Might Promotementioning

confidence: 99%

Barrier Epithelial Cells and the Control of Type 2 Immunity

2015

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Type-2-cell-mediated immunity, rich in eosinophils, basophils, mast cells, CD4(+) T helper 2 (Th2) cells, and type 2 innate lymphoid cells (ILC2s), protects the host from helminth infection but also drives chronic allergic diseases like asthma and atopic dermatitis. Barrier epithelial cells (ECs) represent the very first line of defense and express pattern recognition receptors to recognize type-2-cell-mediated immune insults like proteolytic allergens or helminths. These ECs mount a prototypical response made up of chemokines, innate cytokines such as interleukin-1 (IL-1), IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), as well as the alarmins uric acid, ATP, HMGB1, and S100 proteins. These signals program dendritic cells (DCs) to mount Th2-cell-mediated immunity and in so doing boost ILC2, basophil, and mast cell function. Here we review the general mechanisms of how different stimuli trigger type-2-cell-mediated immunity at mucosal barriers and how this leads to protection or disease.

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“…For example, even in the absence of known lung disease, lung samples from smokers contained increased TSLP levels as compared to nonsmokers (Ying et al 2008 ). In addition, lung epithelial cells from asthmatics produced more TSLP in response to dsRNA (viral analogue) stimulation in culture (Uller et al 2010 ;Brandelius et al 2011 ), which may explain, at least in part, why patients with asthma tend to suffer more airway dysfunction after respiratory infections compared to healthy individuals (Jackson and Johnston 2010 ). This aberrant TSLP production in response to lung insults may thus infl uence both the susceptibility of certain individuals to develop allergic respiratory diseases such as asthma and the clinical complications that arise after environmental insults to the lungs of these individuals.…”

Section: Respiratory Diseasesmentioning

confidence: 99%

Thymic Stromal Lymphopoietin (TSLP)

et al. 2013

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Originally shown to promote the growth and activation of B cells, thymic stromal lymphopoietin (TSLP) is now known to have wide-ranging impacts on both hematopoietic and nonhematopoietic cell lineages, including dendritic cells (DCs), basophils, eosinophils, mast cells, CD4 + , CD8 + , and natural killer (NK) T cells, B cells, and epithelial cells. Although the role of TSLP in the promotion of TH2 responses has been extensively studied in the context of lung-and skin-specifi c allergic disorders, it is becoming increasingly clear that TSLP may impact multiple disease states within multiple organ systems, including the blockade of TH1/TH17 responses and the promotion of cancer and autoimmunity. This review will highlight recent advances in the understanding of TSLP signal transduction, as well as the role of TSLP in allergy, autoimmunity, and cancer. Importantly, these insights into TSLP's multifaceted roles could potentially allow for novel therapeutic manipulations of these disorders.

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dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant

Cited by 38 publications

References 31 publications

Viral Stimuli Trigger Exaggerated Thymic Stromal Lymphopoietin Expression by Chronic Obstructive Pulmonary Disease Epithelium: Role of Endosomal TLR3 and Cytosolic RIG-I-Like Helicases

Viral Stimuli Trigger Exaggerated Thymic Stromal Lymphopoietin Expression by Chronic Obstructive Pulmonary Disease Epithelium: Role of Endosomal TLR3 and Cytosolic RIG-I-Like Helicases

Barrier Epithelial Cells and the Control of Type 2 Immunity

Thymic Stromal Lymphopoietin (TSLP)

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