C-Terminal Region of Caveolin-3 Contains a Stretch of Amino Acid Residues Capable of Diminishing Symptoms of Experimental Autoimmune Encephalomyelitis but Not Rheumatoid Arthritis Modeled in Rats

• Published in: Biomedicines Vol. 11; no. 10; p. 2855
• Main Authors: Danilkovich, Alexey V, Turobov, Valery I, Palikov, Victor A, Palikova, Yulia A, Shepelyakovskaya, Anna O, Mikhaylov, Evgeniy S, Slashcheva, Gulsara A, Shadrina, Tatiana E, Shaykhutdinova, Elvira R, Rasskazova, Ekaterina A, Tukhovskaya, Elena A, Khokhlova, Oksana N, Dyachenko, Igor A, Ismailova, Alina M, Zinchenko, Dmitry V, Navolotskaya, Elena V, Lipkin, Valery M, Murashev, Arkady N, Udovichenko, Igor. P
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-10-2023; MDPI
• Subjects: Amino acids; Antibodies; Antigens; Arthritis; autoimmune disease; Autoimmune diseases; B cells; Caveolin; Cells; Collagen; collagen-induced arthritis (CIA); Cytotoxicity; Disease; drugs; encephalomyelitis (EAE); Epstein-Barr virus; Experimental allergic encephalomyelitis; Glycoproteins; Health aspects; Homology; Immune system; Immunomodulation; Lymphocytes; Major histocompatibility complex; Multiple sclerosis; Nervous system; Pathology; peptide; Peptides; Proteins; Rheumatoid arthritis; Rheumatoid factor; Structure-function relationships; Germany; Russia; United States > US
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11102855

A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure–function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3’s ability to reduce EAE symptoms in Dark Agouti (DA) rats injected with pCav3 (500 µg/kg). pCav3 was found to interfere with the proliferation of lymphocytes extracted from the LNs of DA rats primed with homogenate injection, with IC50 = 0.42 μM (2.35 mcg/mL). pCav3 affected EAE in a very similar manner as immunocortin. The high degree of homology between the amino acid sequences of pCav3 and immunocortin corresponded well with the therapeutic activities of both peptides, as demonstrated on EAE. The latter peptide, possessing a homologous structure to pCav3, was also tested on EAE to explore whether there were structural restrictions between these peptides implied by the MHC-involved cell machinery. Consequently, immunocortin was further examined with a different autoimmune disease model, collagen-induced arthritis (CIA), established in Sprague–Dawley rats. CIA was established using an intentionally different genetic platform than EAE. Based on the results, it was concluded that the effectiveness of pCav3 and immunocortin peptides in EAE rat model was almost identical, but differed in the rat model of rheumatoid arthritis; thus, efficacy may be sensitive to the MHC type of animals used to establish the autoimmune disease model.