Design and validation of anti-inflammatory peptides from human parotid secretory protein.
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.
Geetha
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C
Department of Periodontics, Endodontics and Dental Hygiene, Room 209C, University of Louisville Health Sciences Center, School of Dentistry, Louisville, KY 40292, USA.
Venkatesh
S G
SG
Bingle
L
L
Bingle
C D
CD
Gorr
S-U
SU
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D015202:Protein Engineering / Q000379:methods*; D012313:RNA / Q000032:analysis; D012471:Salivary Proteins and Peptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C485599:BPIFA1 protein, human; C045623:BPIFA2 protein, human; D001798:Blood Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012471:Salivary Proteins and Peptides; D014409:Tumor Necrosis Factor-alpha; C021623:bactericidal permeability increasing protein; D012313:RNA