MTADV 5-MER peptide (5-MP) suppresses chronic inflammations and unveils a new potential target – Serum Amyloid A (SAA)
The peptide (MTADV) targets SAA, that fuels inflammations, and thereby suppresses SAA potency to stimulate the production of pro- inflammatory cytokines
Ma’ayan Shaked1 , Haim Ovadia2 , Keren-Or Amar1, Lora Eshkar –Sebban1 Shmuel Cohen1 , Michal Melamed1 , Jin Ryoun Kim 3 , Hanna Rosenmann4 ,Mary Cowman5, Ehud Cohen6 and David Naor1
1The Lautenberg Center of Immunology and Cancer Research ,Faculty of Medicine, Hebrew University of Jerusalem, Israel; 2Department of Neurology, Hadassah-Hebrew University Medical Center , Jerusalem ,Israel; 3Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, Brooklyn, USA; 4Department of Neurology,The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center; 5Tandon School of Engineering, New York University, New York, NY, USA, 6Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel–Canada, Hebrew University, School of Medicine, Jerusalem, Israel;
A human anti-inflammatory 5-MER peptide (5-MP) MTADV (methionine-threonine-alanine-aspartic acid-valine) was derived from a sequence of a pro-inflammatory CD44 variant. This human peptide displays an efficient anti-inflammatory effect and ameliorates pathology in Collagen-Induced Arthritis (CIA), Inflammatory Bowel Diseases (IBD) and Experimental Autoimmune Encephalomyelitis (EAE), mouse models of Rheumatoid Arthritis (RA), Crohn’s Disease/Ulcerative Colitis and Multiple Sclerosis (MS), respectively. In addition, 5-MP substantially reduces the number of inflammatory Ectopic Lymphoid Structures (ELS) that provide shelter and foster Hepatic Cell Carcinoma (HCC) . In the CIA model, 5-MP was daily IP/SC injected after the onset of disease. In the EAE model the peptide was daily orally delivered. However, using similar protocols, the 5-MP did not inhibit normal immune responses. Mass spectrometric analysis following protein pull down of RA synovial cell extract with biotinylated peptide , revealed that the peptide is bound to SAA in vitro . Additionally, in vivo studies support the suggestion that SAA is a target of the 5-MP. MTADV (but not scrambled TMVAD) significantly inhibited the release of pro-inflammatory cytokines IL-6 , IL-1β and TNFά from SAA-activated human cells .mRNA Bioinformatics and qRT-PCR analyses revealed upregulation of anti-inflammatory and anti-neurodegeneration genes after injection of 5-MP. The peptide disrupted SAA molecular assembly , which is associated with its in vitro and in vivo inflammation suppressive effects. Part of these findings were published in Peer Review journals and enjoyed the Hebrew university 2021 Kaye Prize for scientific innovation. They exhibit the anti-inflammation activity of 5-MP and its potential to ameliorate SAA-associated inflammatory, neurodegenerative and cancer diseases.
The pro-inflammatory activity of Serum Amyloid A (SAA)
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