Abstract
The infiltration, accumulation and degranulation of eosinophils in the lung represents a hallmark of active asthma. In vivo or in vitro eosinophil activation triggers the secretion of the antiapoptotic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). We now identify Pin1, a cis-trans isomerase, as an essential component of the ribonucleoprotein complex responsible for GM-CSF mRNA stabilization, cytokine secretion and the survival of activated eosinophils. Pin1 regulated the association of the AU-rich element-binding proteins AUF1 and hnRNP C with GM-CSF mRNA, accelerating or slowing decay, respectively. These data indicate Pin1 is a key mediator of GM-CSF production.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Allergens / immunology
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Cell Survival / physiology
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Cells, Cultured
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Eosinophils / enzymology*
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Eosinophils / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
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Heterogeneous Nuclear Ribonucleoprotein D0
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Heterogeneous-Nuclear Ribonucleoprotein D / metabolism
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Humans
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Hyaluronic Acid / physiology
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NIMA-Interacting Peptidylprolyl Isomerase
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Peptidylprolyl Isomerase / physiology*
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RNA Stability
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RNA, Messenger / metabolism*
Substances
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Allergens
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HNRNPD protein, human
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Heterogeneous Nuclear Ribonucleoprotein D0
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Heterogeneous-Nuclear Ribonucleoprotein D
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NIMA-Interacting Peptidylprolyl Isomerase
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RNA, Messenger
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Granulocyte-Macrophage Colony-Stimulating Factor
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Hyaluronic Acid
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PIN1 protein, human
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Peptidylprolyl Isomerase