Distinct roles for IL-13 and IL-4 via IL-13 receptor α1 and the type II IL-4 receptor in asthma pathogenesis

Munitz, Ariel; Brandt, Eric B.; Mingler, M K; Finkelman, Fred D.; Rothenberg, Marc E.

doi:10.1073/pnas.0802465105

Cited by 240 publications

(276 citation statements)

References 32 publications

Supporting

Mentioning

253

Contrasting

Unclassified

Order By: Relevance

“…A reason for that may be both cytokines competitively bind to the type II IL-4R receptor that was completely saturated at the concentrations used. Overall, IL-4 had a bigger effect on the CBF than IL-13, possibly because IL-4 additionally binds to the type I IL-4R receptor whereas IL-13 does not (20,24,25). The table shows the mean CBF with sD within the different experiments.…”

Section: Discussionmentioning

confidence: 99%

Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia

et al. 2016

View full text Add to dashboard Cite

Background:In asthmatic airways secondary ciliary dyskinesia contributes to impaired mucociliary clearance. To investigate underlying mechanisms, we studied the effects of cytokines associated with asthma phenotype on the ciliary beat frequency (CBF) in a cell culture model of ciliated human respiratory epithelial cells. Methods: Nasal respiratory epithelial cells of 21 patients were used to prepare multicellular cells (spheroids) in the presence of the T helper (TH) 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13, and the TH1 cytokine interferon gamma (IFN-γ). CBF was determined by high-speed video microscopy. results: Addition of IL-4 and IL-13 and IL-4 + IL-13 decreased the mean CBF by 17, 21, and 22%, respectively, compared with untreated controls. Addition of IL-5 and IL-9 lead to an increase in mean CBF (20 and 10%, respectively). Lower concentrations of IFN-γ (0.1 and 1 ng/ml) decreased mean CBF and higher concentrations (10 ng/ml) increased CBF by 6%. Addition of IFN-γ to IL-13 reversed the effect of IL-13 on the CBF of spheroids. conclusion: Cytokines directly influence the ciliary function of respiratory epithelium and contribute to the impaired mucociliary clearance in asthmatic disease. Our study encourages further research to investigate IFN-γ as a treatment option in diseases with impaired mucociliary clearance like asthma.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Ϫ/Ϫ , and Il13ra2 Ϫ/Ϫ mice (N10 BALB/c) were bred at Cincinnati Children's Hospital Medical Center as described previously (20). All mice were maintained in a barrier facility, and animals were handled under Cincinnati Children's Hospital Medical Center and IACUC-approved protocols.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-13 (IL-13)/IL-13 Receptor α1 (IL-13Rα1) Signaling Regulates Intestinal Epithelial Cystic Fibrosis Transmembrane Conductance Regulator Channel-dependent Cl− Secretion

Wu¹,

Ahrens²,

Osterfeld³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Interleukin-13 (IL-13) has been linked to the pathogenesis of inflammatory diseases of the gastrointestinal tract. It is postulated that IL-13 drives inflammatory lesions through the modulation of both hematopoietic and nonhematopoietic cell function in the intestine. To delineate the relevant contribution of elevated levels of intestinal IL-13 to intestinal structure and function, we generated an intestinal IL-13 transgenic mouse (iIL-13Tg). We show that constitutive overexpression of IL-13 in the small bowel induces modification of intestinal epithelial architecture (villus blunting, goblet cell hyperplasia, and increased epithelial proliferation) and epithelial function (altered basolateral 3 apical Cl ؊ ion conductance). Pharmacological analyses in vitro and in vivo determined that elevated Cl

show abstract

“…As a cause of airway inflammation and asthma, IL-4 has been considered to be the best therapeutic target in asthma. However, several clinical and fundamental studies have demonstrated that IL-9 and IL-13 are more important cytokines in the onset of allergic asthma than IL-4 (13,(42)(43)(44). Moreover, it was also demonstrated that IL-9 induces IL-13 expression in airway epithelial cells and promotes airway inflammation (45).…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide and Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway Promote IL-9 Production in Th9 Differentiation Process

Mikami

Miyagi

Sueda

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Th9 cells are a novel Th cell subset that produces IL-9 and is involved in type I hypersensitivity such as airway inflammation. Although its critical roles in asthma have attracted interest, the physiological regulatory mechanisms of Th9 cell differentiation and function are largely unknown. Asthma is easily affected by psychological factors. Therefore, we investigated one of the physiological mediators derived from the nervous system, calcitonin gene-related peptide (CGRP), in asthma and Th9 cells because CGRP and activation of the cAMP/protein kinase A (PKA) pathway by CGRP are known to be important regulators in several immune responses and allergic diseases. In this study, we demonstrated that the CGRP/cAMP/PKA pathway promotes IL-9 production via NFATc2 activation by PKA-dependent glycogen synthase kinase-3β inactivation. Moreover, CGRP also induces the expression of PU.1, a critical transcriptional factor in Th9 cells, which depends on PKA, but not NFATc2. Additionally, we demonstrated the physiological importance of CGRP in IL-9 production and Th9 differentiation using an OVA-induced airway inflammation model and T cell–specific CGRP receptor-deficient mice. The present study revealed a novel regulatory mechanism comprising G protein–coupled receptor ligands and nervous system-derived substances in Th9 cell differentiation and type I hypersensitivity.

show abstract

Distinct roles for IL-13 and IL-4 via IL-13 receptor α1 and the type II IL-4 receptor in asthma pathogenesis

Abstract: inflammation ͉ cytokines ͉ eosinophils ͉ chemokines ͉ mucus

Cited by 240 publications

References 32 publications

Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia

Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia

Interleukin-13 (IL-13)/IL-13 Receptor α1 (IL-13Rα1) Signaling Regulates Intestinal Epithelial Cystic Fibrosis Transmembrane Conductance Regulator Channel-dependent Cl− Secretion

Calcitonin Gene-Related Peptide and Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway Promote IL-9 Production in Th9 Differentiation Process

Contact Info

Product

Resources

About