Immunotherapeutic potential of collagen V oral administration in mBSA/CFA-induced arthritis

Author:

Silveira Lizandre Keren Ramos da1,Velosa Ana Paula1,Catanozi Sergio2,Pereira Marco Aurélio A.3,Filho Antonio dos Santos1,Marques Fabio Luiz N.4,Faria Daniele de Paula4,Real Caroline Cristiano4,Fernezlian Sandra de M.5,Yanke Amanda Flores6,Queiroz Zelita Aparecida de J.6,Contini Vitória Elias6,Lobo Thays de Matos6,Carrasco Solange6,Baldavira Camila Machado5,Goldenstein-Schainberg Cláudia6,Fuller Ricardo6,Capelozzi Vera L.5,Teodoro Walcy R.6

Affiliation:

1. Division of Rheumatology, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo-SP, Brazil

2. Laboratorio de Lipides (LIM-10), Hospital das Clinicas (HCFMUSP) da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo 01246-000, Brazil

3. Department of Surgery, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo, Brazil, 05508-270

4. Laboratory of Nuclear Medicine (LIM 43), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR, 05403-911

5. Department of Pathology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil, 01246-903

6. Division of Rheumatology, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo-SP, Brazil, 01246-903

Abstract

Abstract

We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 µg/300 µL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 µL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10 + and FoxP3 + cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Springer Science and Business Media LLC

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