A novel anti-inflammatory peptide from human lipocortin 5.
1. A novel anti-inflammatory peptide (residues 204-212) of human recombinant lipocortin 5 (hrLC5) found on the high similarity region with uteroglobin is described. 2. Peptide 204-212 dose-dependently inhibited the contractions of rat isolated stomach strips elicited by porcine pancreatic phospholipase A2 (PLA2). Contractions caused by arachidonic acid (AA), prostaglandin E2 (PGE2) and 5-hydroxytryptamine were not affected. No direct enzyme inhibition was observed in a radiochemical assay. 3. PGE2 release by both human fibroblasts and rat macrophages was reduced by peptide 204-212 in a dose-dependent manner. 4. The development of carrageenin-induced oedema in rats was significantly inhibited by the local administration of peptide 204-212. 5. The pattern and potency of the biological effects of peptide 204-212 are similar to those of antiflammin 2, a lipocortin 1-derived peptide. 6. It is suggested that peptide 204-212 may represent the active site responsible for the anti-inflammatory properties of lipocortin 5.
Perretti
M
M
Sclavo Research Centre, Laboratory of Pharmacology, Siena, Italy.
Becherucci
C
C
Mugridge
K G
KG
Solito
E
E
Silvestri
S
S
Parente
L
L
D000595:Amino Acid Sequence; D000818:Animals; D017304:Annexin A5; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000494:pharmacology*; D002351:Carrageenan; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011257:Pregnancy Proteins / Q000032:analysis / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000032:analysis / Q000494:pharmacology; D016415:Sequence Alignment; D014598:Uteroglobin / Q000032:analysis
D017304:Annexin A5; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002135:Calcium-Binding Proteins; D010455:Peptides; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D002351:Carrageenan; D014598:Uteroglobin; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone