Myeloid differentiation protein 2 facilitates pollen- and cat dander-induced innate and allergic airway inflammation

Koa Hosoki, Istvan Boldogh, Leopoldo Aguilera-Aguirre, Qian Sun, Toshiko Itazawa, Tapas Hazra, Allan R. Brasier, Alexander Kurosky, Sanjiv Sur

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background The National Health and Nutrition Examination Survey identified several pollens and cat dander as among the most common allergens that induce allergic sensitization and allergic diseases. We recently reported that ragweed pollen extract (RWPE) requires Toll-like receptor 4 (TLR4) to stimulate CXCL-mediated innate neutrophilic inflammation, which in turn facilitates allergic sensitization and airway inflammation. Myeloid differentiation protein 2 (MD2) is a TLR4 coreceptor, but its role in pollen- and cat dander-induced innate and allergic inflammation has not been critically evaluated. Objective We sought to elucidate the role of MD2 in inducing pollen- and cat dander-induced innate and allergic airway inflammation. Methods TCMNull (TLR4Null, CD14Null, MD2Null), TLR4Hi, and TCMHi cells and human bronchial epithelial cells with small interfering RNA-induced downregulation of MD2 were stimulated with RWPE, other pollen allergic extracts, or cat dander extract (CDE), and activation of nuclear factor κB (NF-κB), secretion of the NF-κB-dependent CXCL8, or both were quantified. Wild-type mice or mice with small interfering RNA knockdown of lung MD2 were challenged intranasally with RWPE or CDE, and innate and allergic inflammation was quantified. Results RWPE stimulated MD2-dependent NF-κB activation and CXCL secretion. Likewise, Bermuda, rye, timothy, pigweed, Russian thistle, cottonwood, walnut, and CDE stimulated MD2-dependent CXCL secretion. RWPE and CDE challenge induced MD2-dependent and CD14-independent innate neutrophil recruitment. RWPE induced MD2-dependent allergic sensitization and airway inflammation. Conclusions MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.

Original languageEnglish (US)
Pages (from-to)1506-1513.e2
JournalJournal of Allergy and Clinical Immunology
Volume137
Issue number5
DOIs
StatePublished - May 1 2016

Fingerprint

Dander
Pollen
Cats
Inflammation
Proteins
Toll-Like Receptor 4
Small Interfering RNA
Salsola
Bermuda
Juglans
Populus
Neutrophil Infiltration
Nutrition Surveys
Allergens
ragweed pollen
Down-Regulation
Epithelial Cells

Keywords

  • antigen
  • cat dander
  • Key words Allergic inflammation
  • MD2
  • neutrophil
  • nuclear factor κB
  • pollen
  • ragweed
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Myeloid differentiation protein 2 facilitates pollen- and cat dander-induced innate and allergic airway inflammation. / Hosoki, Koa; Boldogh, Istvan; Aguilera-Aguirre, Leopoldo; Sun, Qian; Itazawa, Toshiko; Hazra, Tapas; Brasier, Allan R.; Kurosky, Alexander; Sur, Sanjiv.

In: Journal of Allergy and Clinical Immunology, Vol. 137, No. 5, 01.05.2016, p. 1506-1513.e2.

Research output: Contribution to journalArticle

Hosoki, Koa ; Boldogh, Istvan ; Aguilera-Aguirre, Leopoldo ; Sun, Qian ; Itazawa, Toshiko ; Hazra, Tapas ; Brasier, Allan R. ; Kurosky, Alexander ; Sur, Sanjiv. / Myeloid differentiation protein 2 facilitates pollen- and cat dander-induced innate and allergic airway inflammation. In: Journal of Allergy and Clinical Immunology. 2016 ; Vol. 137, No. 5. pp. 1506-1513.e2.
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abstract = "Background The National Health and Nutrition Examination Survey identified several pollens and cat dander as among the most common allergens that induce allergic sensitization and allergic diseases. We recently reported that ragweed pollen extract (RWPE) requires Toll-like receptor 4 (TLR4) to stimulate CXCL-mediated innate neutrophilic inflammation, which in turn facilitates allergic sensitization and airway inflammation. Myeloid differentiation protein 2 (MD2) is a TLR4 coreceptor, but its role in pollen- and cat dander-induced innate and allergic inflammation has not been critically evaluated. Objective We sought to elucidate the role of MD2 in inducing pollen- and cat dander-induced innate and allergic airway inflammation. Methods TCMNull (TLR4Null, CD14Null, MD2Null), TLR4Hi, and TCMHi cells and human bronchial epithelial cells with small interfering RNA-induced downregulation of MD2 were stimulated with RWPE, other pollen allergic extracts, or cat dander extract (CDE), and activation of nuclear factor κB (NF-κB), secretion of the NF-κB-dependent CXCL8, or both were quantified. Wild-type mice or mice with small interfering RNA knockdown of lung MD2 were challenged intranasally with RWPE or CDE, and innate and allergic inflammation was quantified. Results RWPE stimulated MD2-dependent NF-κB activation and CXCL secretion. Likewise, Bermuda, rye, timothy, pigweed, Russian thistle, cottonwood, walnut, and CDE stimulated MD2-dependent CXCL secretion. RWPE and CDE challenge induced MD2-dependent and CD14-independent innate neutrophil recruitment. RWPE induced MD2-dependent allergic sensitization and airway inflammation. Conclusions MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.",
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T1 - Myeloid differentiation protein 2 facilitates pollen- and cat dander-induced innate and allergic airway inflammation

AU - Hosoki, Koa

AU - Boldogh, Istvan

AU - Aguilera-Aguirre, Leopoldo

AU - Sun, Qian

AU - Itazawa, Toshiko

AU - Hazra, Tapas

AU - Brasier, Allan R.

AU - Kurosky, Alexander

AU - Sur, Sanjiv

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AB - Background The National Health and Nutrition Examination Survey identified several pollens and cat dander as among the most common allergens that induce allergic sensitization and allergic diseases. We recently reported that ragweed pollen extract (RWPE) requires Toll-like receptor 4 (TLR4) to stimulate CXCL-mediated innate neutrophilic inflammation, which in turn facilitates allergic sensitization and airway inflammation. Myeloid differentiation protein 2 (MD2) is a TLR4 coreceptor, but its role in pollen- and cat dander-induced innate and allergic inflammation has not been critically evaluated. Objective We sought to elucidate the role of MD2 in inducing pollen- and cat dander-induced innate and allergic airway inflammation. Methods TCMNull (TLR4Null, CD14Null, MD2Null), TLR4Hi, and TCMHi cells and human bronchial epithelial cells with small interfering RNA-induced downregulation of MD2 were stimulated with RWPE, other pollen allergic extracts, or cat dander extract (CDE), and activation of nuclear factor κB (NF-κB), secretion of the NF-κB-dependent CXCL8, or both were quantified. Wild-type mice or mice with small interfering RNA knockdown of lung MD2 were challenged intranasally with RWPE or CDE, and innate and allergic inflammation was quantified. Results RWPE stimulated MD2-dependent NF-κB activation and CXCL secretion. Likewise, Bermuda, rye, timothy, pigweed, Russian thistle, cottonwood, walnut, and CDE stimulated MD2-dependent CXCL secretion. RWPE and CDE challenge induced MD2-dependent and CD14-independent innate neutrophil recruitment. RWPE induced MD2-dependent allergic sensitization and airway inflammation. Conclusions MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.

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KW - ragweed

KW - Toll-like receptor 4

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