title: Myeloid differentiation protein 2 facilitates pollen- and cat dander-induced innate and allergic airway inflammation.
abstract: 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.
  
  
  
  We sought to elucidate the role of MD2 in inducing pollen- and cat dander-induced innate and allergic airway inflammation.
  
  
  
  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.
  
  
  
  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.
  
  
  
  MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.
authors.affiliation: Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Medical Branch, Galveston, Tex.
authors.forename: Koa
authors.initials: K
authors.lastname: Hosoki
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Tex; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Tex.
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Tex.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Aguilera-Aguirre
authors.affiliation: Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Medical Branch, Galveston, Tex.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Medical Branch, Galveston, Tex.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Itazawa
authors.affiliation: Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Tex; Department of Internal Medicine, Division of Pulmonary Critical Care & Sleep Medicine, University of Texas Medical Branch, Galveston, Tex.
authors.forename: Tapas
authors.initials: T
authors.lastname: Hazra
authors.affiliation: Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Medical Branch, Galveston, Tex; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Tex.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Brasier
authors.affiliation: Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Tex; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Tex.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurosky
authors.affiliation: Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Medical Branch, Galveston, Tex; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Tex. Electronic address: sasur@UTMB.edu.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Sur
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002415:Cats / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D063607:Dander / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D010936:Plant Extracts / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology*
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D009077:Mucins; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; C433085:ragweed pollen
keywords: Allergic inflammation; MD2; Toll-like receptor 4; antigen; cat dander; neutrophil; nuclear factor κB; pollen; ragweed