Physical exercise contributes to cisplatin-induced nephrotoxicity protection with decreased CD4+T cells activation

Autor(es):Mostrar menos -

Saito Miyagi, Mariana Yasue ^[1] ; Latancia, Marcela Teatin ^{[1, 2]} ; Testagrossa, Leonardo Abreu ^[3] ; de Andrade-Oliveira, Vinicius ^[1] ; Pereira, Welbert Oliveira ^[4] ; Hiyane, Meire Ioshie ^[1] ; Enjiu, Lucas Maceratesi ^[5] ; Pisciottano, Marcus ^[5] ; Leite Seelaender, Marilia Cerqueira ^[5] ; Saraiva Camara, Niels Olsen ^{[1, 6]} ; Amano, Mariane Tami ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Immunobiol Transplants, Sao Paulo, SP - Brazil

^[2] Hosp Sirio Libanes, Inst Sirio Libanes Ensino & Pesquisa, Rua Daher Cutait, 69 7SS Bloco D, BR-01308060 Sao Paulo, SP - Brazil

^[3] Hosp Sirio Libanes, Clin Pathol Lab, Sao Paulo, SP - Brazil

^[4] Hosp Israelita Albert Einstein, Fac Israelita Ciencias Saude Albert Einstein, Sch Med, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Cell Biol, Lab Lipid Metab, Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Fac Med, Lab Renal Pathol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Immunology; v. 101, p. 507-513, SEP 2018.
• Citações Web of Science: 0

Resumo

Cisplatin is a chemotherapy used to treat different types of cancer, such as testicular, bladder and head and neck. Physical exercise has been shown to improve cancer therapy and recently, it was demonstrated to be able to diminish side effects such as acute kidney injury (AKI), a common side effect in cisplatin treatment. In both cases, the modulation of inflammatory cytokines seems to be one of the mechanisms, but little is known about the immune cells in this process. Here, we investigated the role of CD4 + T cells in the AKI protection by physical exercise. We subjected C57B16 mice to long-term physical exercise (EX) before cisplatin treatment. Sedentary groups were used as control (CT). We confirmed that physical exercise decreased AKI by evaluating creatinine and Kim-1 levels, in the serum and kidney respectively. Analyzing the organs weight, we noticed a decrease in sedentary (CIS) and exercised (CIS-EX) cisplatin treated groups. Epididymal and brown adipose tissue weight were decreased in cisplatin treated subjects in comparison to untreated groups, as well as liver and spleen. We then investigated the profile of CD4 + T cells in the spleen and we observed increased levels of Tregs and CD4 + CD25 + cells in CIS group, while CIS-EX presented similar amounts as control groups. Analyzing the kidney lymph nodes, we noticed a decrease of CD4 + cells in both CIS and CIS-EX group. However, a more activated phenotype (CD69 + and CD25 + ) was observed in CIS groups in comparison to CIS-EX group, as well as the presence of Tregs. We then investigated the production of cytokines by these cells and no difference among the groups was observed in cytokines production in splenic CD4 + T cells. However, a clear increase in TNF and IL-10 production was observed in CD4 + T cells from lymph nodes, while CIS-EX group presented similar levels as the control groups. We confirmed that physical exercise was able to diminish cisplatin-induced AKI with concomitant decrease in CD4 + T cell activation. (AU)

• Processo FAPESP: 12/50079-0 - Inflamação sistêmica em pacientes com caquexia associada ao câncer: mecanismos e estratégias terapêuticas, uma abordagem em medicina translacional
• Beneficiário: Marilia Cerqueira Leite Seelaender
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/10349-5 - O papel do exercício físico na lesão renal induzida pela cisplatina
• Beneficiário: Mariana Yasue Saito Miyagi
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 12/10435-1 - A influência da via mtor na modulação de macrófagos e suas consequências na doença renal crônica experimental
• Beneficiário: Mariane Tami Amano
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/02270-2 - Novos mecanismos celulares, moleculares e imunológicos das lesões renais agudas e crônicas: busca por novas estratégias terapêuticas
• Beneficiário: Niels Olsen Saraiva Câmara
• Linha de fomento: Auxílio à Pesquisa - Temático