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

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• 作者：Koa Hosoki ; MD ; PhD^a ; Istvan Boldogh ; PhD^b ; ^c ; Leopoldo Aguilera-Aguirre ; PhD^b ; Qian Sun ; PhD^a ; Toshiko Itazawa ; MD ; PhD^a ; Tapas Hazra ; PhD^c ; ^d ; Allan R. Brasier ; MD^a ; ^c ; Alexander Kurosky ; PhD^c ; ^e ; Sanjiv Sur ; MD^a ; ^c ; ^{sasur@UTMB.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Allergic inflammation ; antigen ; cat dander ; pollen ; MD2 ; neutrophil ; nuclear factor κB ; ragweed ; Toll-like receptor 4
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：137
• 期：5
• 页码：1506-1513.e2
• 全文大小：1577 K

文摘

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

TCM^Null (TLR4^Null, CD14^Null, MD2^Null), TLR4^Hi, and TCM^Hi 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.