The Crotoxin:SBA-15 Complex Down-Regulates the Incidence and Intensity of Experimental Autoimmune Encephalomyelitis Through Peripheral and Central Actions

Author(s):Show less -

Sant'Anna, Morena Brazil ^[1] ; Giardini, Aline C. ^[1] ; Ribeiro, Marcio A. C. ^[2] ; Lopes, Flavia S. R. ^[1] ; Teixeira, Nathalia B. ^[1] ; Kimura, Louise F. ^[1] ; Bufalo, Michelle C. ^[1] ; Ribeiro, Orlando G. ^[3] ; Borrego, Andrea ^[3] ; Cabrera, Wafa H. K. ^[3] ; Ferreira, Julio C. B. ^{[2, 4]} ; Zambelli, Vanessa O. ^{[5, 1]} ; Sant'Anna, Osvaldo A. ^[6] ; Picolo, Gisele ^[1]

Affiliation

^[1] Butantan Inst, Lab Pain & Signaling, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo - Brazil

^[3] Butantan Inst, Immunogenet Lab, Sao Paulo - Brazil

^[4] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA - USA

^[5] Stanford Univ, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Stanford, CA 94305 - USA

^[6] Butantan Inst, Lab Immunochem, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 11, OCT 28 2020.
• Web of Science Citations: 0

Abstract

Crotoxin (CTX), the main neurotoxin from Crotalus durissus terrificus snake venom, has anti-inflammatory, immunomodulatory and antinociceptive activities. However, the CTX-induced toxicity may compromise its use. Under this scenario, the use of nanoparticle such as nanostructured mesoporous silica (SBA-15) as a carrier might become a feasible approach to improve CTX safety. Here, we determined the benefits of SBA-15 on CTX-related neuroinflammatory and immunomodulatory properties during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis that replicates several histopathological and immunological features observed in humans. We showed that a single administration of CTX:SBA-15 (54 mu g/kg) was more effective in reducing pain and ameliorated the clinical score (motor impairment) in EAE animals compared to the CTX-treated EAE group; therefore, improving the disease outcome. Of interest, CTX:SBA-15, but not unconjugated CTX, prevented EAE-induced atrophy and loss of muscle function. Further supporting an immune mechanism, CTX:SBA-15 treatment reduced both recruitment and proliferation of peripheral Th17 cells as well as diminished IL-17 expression and glial cells activation in the spinal cord in EAE animals when compared with CTX-treated EAE group. Finally, CTX:SBA-15, but not unconjugated CTX, prevented the EAE-induced cell infiltration in the CNS. These results provide evidence that SBA-15 maximizes the immunomodulatory and anti-inflammatory effects of CTX in an EAE model; therefore, suggesting that SBA-15 has the potential to improve CTX effectiveness in the treatment of MS. (AU)

• FAPESP's process: 17/17844-8 - Nanostructured silica as a protective vehicle for vaccines and biomolecules
• Grantee: Osvaldo Augusto Brazil Esteves Sant'Anna
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/01254-1 - Evaluating the effect of crotoxin-nanostructured silica SBA-15 complex in chronic pain: immunomodulatory, antinociceptive and antiinflammatory aspects
• Grantee: Gisele Picolo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/19397-0 - Evaluating the effect of crotoxin conjugated nanostructured silica SBA-15 in chronic pain: immunomodulatory, antinociceptive and antiinflammatory aspects
• Grantee: Morena Brazil Martins Sant'Anna
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC