Systemic Administration of Proteoglycan Protects BALB/c Retired Breeder Mice from Experimental Arthritis.
This study was undertaken to evaluate the prophylactic potential of proteoglycan (PG) administration in experimental arthritis. Female BALB/c retired breeder mice received two (2xPG50 and 2xPG100 groups) or three (3xPG50 group) intraperitoneal doses of bovine PG (50 μg or 100 μg) every three days. A week later the animals were submitted to arthritis induction by immunization with three i.p. doses of bovine PG associated with dimethyldioctadecylammonium bromide adjuvant at intervals of 21 days. Disease severity was daily assessed after the third dose by score evaluation. The 3xPG50 group showed significant reduction in prevalence and clinical scores. This protective effect was associated with lower production of IFN-γ and IL-17 and increased production of IL-5 and IL-10 by spleen cells restimulated in vitro with PG. Even though previous PG administration restrained dendritic cells maturation this procedure did not alter the frequency of regulatory Foxp3(+) T cells. Lower TNF-α and IL-6 levels and higher expression of ROR-γ and GATA-3 were detected in the paws of protected animals. A delayed-type hypersensitivity reaction confirmed specific tolerance induction. Taken together, these results indicate that previous PG inoculation determines a specific tolerogenic effect that is able to decrease severity of subsequently induced arthritis.
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), 18618-689 Botucatu, SP, Brazil.
Larissa Lumi Watanabe
LL
Ishikawa
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), 18618-689 Botucatu, SP, Brazil.
Priscila Maria
PM
Colavite
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), 18618-689 Botucatu, SP, Brazil.
Thais Fernanda de Campos
TF
Fraga-Silva
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), 18618-689 Botucatu, SP, Brazil.
Luiza Ayumi Nishiyama
LA
Mimura
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), 18618-689 Botucatu, SP, Brazil.
Thais Graziela Donegá
TG
França
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), 18618-689 Botucatu, SP, Brazil.
Sofia Fernanda Gonçalves
SF
Zorzella-Pezavento
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), 18618-689 Botucatu, SP, Brazil.
Fernanda
F
Chiuso-Minicucci
Department of Pathology, Botucatu Medical School, 18618-970 Botucatu, SP, Brazil.
Larissa Doddi
LD
Marcolino
Laboratory of Flow Cytometry, Amaral Carvalho Foundation, 17210-120 Jaú, SP, Brazil.
Camila
C
Marques
Laboratory of Flow Cytometry, Amaral Carvalho Foundation, 17210-120 Jaú, SP, Brazil.
Maura Rosane Valerio
MR
Ikoma
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), 18618-689 Botucatu, SP, Brazil.
Alexandrina
A
Sartori
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D020011:Protective Agents / Q000008:administration & dosage*; D011509:Proteoglycans / Q000008:administration & dosage*; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D020011:Protective Agents; D011509:Proteoglycans; D014157:Transcription Factors