Abstract
To explore regulation of potentially lethal responses to bacterial lipopolysaccharide (LPS), we used differential display under LPS-free conditions to compare macrophage cell lines from two strains of mice congenic for a locus affecting LPS sensitivity. LPS-hyporesponsive cells, primary macrophages, and polymorphonuclear leukocytes transcribed secretory leukocyte protease inhibitor (SLPI), a known epithelial cell-derived inhibitor of leukocyte serine proteases. Transfection of macrophages with SLPI suppressed LPS-induced activation of NF-kappa B and production of nitric oxide and TNF alpha. The ability of interferon-gamma (IFN gamma) to restore LPS responsiveness is a hallmark of the LPS-hyporesponsive phenotype. IFN gamma suppressed expression of SLPI and restored LPS responsiveness to SLPI-producing cells. Thus, SLPI is an LPS-induced IFN gamma-suppressible phagocyte product that serves to inhibit LPS responses.
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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Amino Acid Sequence
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Animals
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Cell Differentiation / drug effects
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Cell Line
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Cloning, Molecular
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Female
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Immunosuppressive Agents / pharmacology
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Interferon-gamma / pharmacology
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Lipopolysaccharides / antagonists & inhibitors*
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Lipopolysaccharides / pharmacology*
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / metabolism*
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Mice
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Mice, Inbred C3H
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Molecular Sequence Data
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Neutrophils / metabolism
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Organ Specificity
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Protein Biosynthesis*
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Proteinase Inhibitory Proteins, Secretory
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Proteins / genetics
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Proteins / pharmacology*
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Secretory Leukocyte Peptidase Inhibitor
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Serine Proteinase Inhibitors / biosynthesis*
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Serine Proteinase Inhibitors / genetics
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Serine Proteinase Inhibitors / pharmacology*
Substances
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Immunosuppressive Agents
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Lipopolysaccharides
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Proteinase Inhibitory Proteins, Secretory
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Proteins
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Secretory Leukocyte Peptidase Inhibitor
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Serine Proteinase Inhibitors
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Slpi protein, mouse
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Interferon-gamma
Associated data
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GENBANK/U73004
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GENBANK/X04502