Anti-inflammatory effects of peptide fragments of H2A histone and Oryza Sativa Japonica protein.
Anti-inflammatory drugs are often of limited use due to low efficacy and toxic effects. The present study describes the anti-inflammatory effects of a novel nonapeptide termed IIIM1, using the mouse hind paw edema as an experimental model of inflammation. Multiple prophylactic injections of IIIM1 resulted in a significant reduction in carrageenan-induced foot pad swelling, both in mice and rats. A single prophylactic treatment of the peptide caused the maximal effect at 7-9 days between the initial peptide treatment and the subsequent carrageenan injection. A reduced inflammatory reaction was observed in transgenic mice constitutively expressing the peptide. A marked decrease in oxidative burst was observed in activated peritoneal macrophages obtained from peptide-treated mice. Furthermore, the sera of IIIM1-treated mice caused a significant decrease in the oxidative burst of macrophages. In addition, the reduction of hind paw swelling in mice injected with the sera of IIIM1-treated mice strongly suggests the presence of a circulating inducible factor responsible for the anti-inflammatory effect of the peptide. Previous LC/MS/MS analysis revealed the presence of a new peptide, termed RA1, in the sera of IIIM1-treated mice. RA1 was identified as a fragment of the Oryza Sativa Japonica protein. The anti-inflammatory effect of RA1 as evidenced by the reduction in carrageenan-induced hind paw swelling corresponded with the decrease in the oxidative burst of macrophages treated in vitro with this peptide. In conclusion, both IIIM1 and RA1 represent potential agents for the efficient treatment of inflammatory diseases that are currently incurable using presently available drugs.
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
Yonatan
Y
Schussheim
Michael
M
Aschner
Berta
B
Brodsky
Elena
E
Proscura
Avigail
A
Erlanger-Rosengarten
Rachel
R
Feldman
Elena
E
Shapira
Uri
U
Wormser
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced; D006657:Histones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012275:Oryza / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010940:Plant Proteins / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats
D000893:Anti-Inflammatory Agents; D006657:Histones; D010446:Peptide Fragments; D010940:Plant Proteins; C559119:RA1 peptide, Oryza sativa; C530140:lysyl-glycyl-histidyl-tyrosyl-alanyl-glutamyl-arginyl-valyl-glyine; D002351:Carrageenan