Abstract
Innate immunity has been extended to respond environmental pathogen other than microbial components. Here we explore a novel pollen/TLR4 innate immunity in allergic inflammation. In experimental allergic conjunctivitis induced by short ragweed (SRW) pollen, typical allergic signs, stimulated IL-33/ST2 signaling and overproduced Th2 cytokine were observed in ocular surface, cervical lymph nodes and isolated CD4+ T cells of BALB/c mice. These clinical, cellular and molecular changes were significantly reduced/eliminated in TLR4 deficient (Tlr4-d) or MyD88 knockout (MyD88-/-) mice. Aqueous SRW extract (SRWe) directly stimulated IL-33 mRNA and protein expression by corneal epithelium and conjunctiva in wild type, but not in Tlr4-d or MyD88-/- mice with topical challenge. Furthermore, SRWe-stimulated IL-33 production was blocked by TLR4 antibody and NF-kB inhibitor in mouse and human corneal epithelial cells. These findings for the first time uncovered a novel mechanism by which SRW pollen initiates TLR4-dependent IL-33/ST2 signaling that triggers Th2-dominant allergic inflammation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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Antigens, Plant / immunology*
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Antigens, Plant / metabolism
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Cells, Cultured
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Conjunctiva / drug effects
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Conjunctiva / metabolism
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Conjunctiva / pathology
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Conjunctivitis, Allergic / etiology
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Conjunctivitis, Allergic / immunology
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Conjunctivitis, Allergic / metabolism
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Cornea / drug effects
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Cornea / metabolism
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Cornea / pathology
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Cytokines / analysis
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Cytokines / genetics
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Cytokines / metabolism
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Female
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Humans
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Immunity, Innate / drug effects*
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Interleukin-1 Receptor-Like 1 Protein / genetics
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Interleukin-1 Receptor-Like 1 Protein / metabolism*
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Interleukin-33 / genetics
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Interleukin-33 / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Middle Aged
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Myeloid Differentiation Factor 88 / deficiency
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Myeloid Differentiation Factor 88 / genetics
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Plant Extracts / immunology*
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Plant Extracts / metabolism
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Plant Extracts / toxicity
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Signal Transduction
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Th2 Cells / cytology
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Th2 Cells / immunology*
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Toll-Like Receptor 4 / deficiency
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / metabolism*
Substances
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Antigens, Plant
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Cytokines
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Il1rl1 protein, mouse
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-33
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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NF-kappa B
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Plant Extracts
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Toll-Like Receptor 4
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ragweed pollen