Abstract
Parotid secretory protein (PSP) and palate-lung-nasal epithelium clone (PLUNC) are novel secretory proteins that are expressed in the oral cavity and upper airways. Both proteins are related to bactericidal/permeability increasing protein (BPI). Cationic peptides derived from BPI exhibit anti-inflammatory activity. To test if PSP (C20orf70 gene product) also contains anti-inflammatory peptides, we designed 3 cationic peptides based on the predicted structure of PSP and known active regions of BPI. Each peptide inhibited the lipopolysaccharide (LPS)-stimulated secretion of TNFalpha from RAW 264.7 macrophage cells. At 200 microg/mL, the peptide GK-7 exhibited inhibition similar to that achieved with 10 microg/mL of polymyxin B. PSP peptides directly inhibited the binding of LPS to LPS-binding protein. The cationic peptide Substance P had no inhibitory effect in these assays, confirming the specificity of the PSP peptides. These findings suggest that PSP peptides can serve as templates for the design of novel anti-inflammatory peptides.
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.
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Validation Study
MeSH terms
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Amino Acid Sequence
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Analysis of Variance
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Anti-Bacterial Agents / chemistry
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Antimicrobial Cationic Peptides / chemical synthesis*
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Antimicrobial Cationic Peptides / pharmacology
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Blood Proteins / chemistry*
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Blood Proteins / genetics
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Cell Line
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Cloning, Molecular
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Glycoproteins / chemistry*
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Glycoproteins / genetics
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Glycoproteins / pharmacology
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Humans
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Macrophages / cytology
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Macrophages / drug effects
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Membrane Proteins / chemistry*
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Membrane Proteins / genetics
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Molecular Sequence Data
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Phosphoproteins / chemistry*
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Phosphoproteins / genetics
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Phosphoproteins / pharmacology
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Protein Engineering / methods*
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RNA / analysis
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Salivary Proteins and Peptides / chemistry*
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Salivary Proteins and Peptides / genetics
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Salivary Proteins and Peptides / pharmacology
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Sequence Alignment
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Sequence Analysis, Protein
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Tumor Necrosis Factor-alpha / drug effects
Substances
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Anti-Bacterial Agents
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Antimicrobial Cationic Peptides
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BPIFA1 protein, human
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BPIFA2 protein, human
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Blood Proteins
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Glycoproteins
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Membrane Proteins
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Phosphoproteins
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Salivary Proteins and Peptides
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Tumor Necrosis Factor-alpha
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bactericidal permeability increasing protein
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RNA