Abstract
The collectin surfactant protein-A (SP-A) is involved in the innate host defense and the regulation of inflammatory processes in the lung. In this work we investigated the molecular mechanisms related to the immunostimulatory activity of SP-A using macrophages from C3H/HeJ mice, which carry an inactivating mutation in the Toll-like receptor (TLR)4 gene, and TLR4-transfected Chinese hamster ovary cells. We demonstrate that SP-A-induced activation of the NF-kappaB signaling pathway and up-regulation of cytokine synthesis such as TNF-alpha and IL-10 are critically dependent on the TLR4 functional complex. These findings support the concept that TLR4 is a pattern recognition receptor that signals in response to both foreign pathogens and endogenous host mediators.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / physiology*
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Animals
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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CHO Cells
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Cricetinae
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Cytokines / metabolism
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Drosophila Proteins*
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Female
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Humans
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Macrophages / immunology
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Macrophages / metabolism
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C3H
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NF-kappa B / metabolism
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NF-kappa B / physiology
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Proteolipids / physiology*
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Pulmonary Surfactant-Associated Protein A
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Pulmonary Surfactant-Associated Proteins
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Pulmonary Surfactants / physiology*
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Receptors, Cell Surface / physiology*
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Signal Transduction / immunology
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Toll-Like Receptor 4
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Toll-Like Receptors
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U937 Cells
Substances
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Adjuvants, Immunologic
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Cytokines
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Drosophila Proteins
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Membrane Glycoproteins
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NF-kappa B
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Proteolipids
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Pulmonary Surfactant-Associated Protein A
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Pulmonary Surfactant-Associated Proteins
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Pulmonary Surfactants
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Receptors, Cell Surface
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TLR4 protein, human
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Toll-Like Receptor 4
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Toll-Like Receptors