Cytokine and Adhesion Molecule Expression Induced by Different Strains of Staphylococcus aureus in Type 1 Diabetic Rats: Role of Insulin

Autor(es)

Knox de Souza, Paula R. ^{[1, 2]} ; Ferreira, Sabrina S. ^[2] ; Nunes, Fernanda P. B. ^[2] ; Casagrande, Felipe B. ^[2] ; Tessaro, Fernando H. G. ^[2] ; Silva, Mariana C. F. ^[2] ; Miranda Costa Cruz, Jose Walber ^[3] ; Mamizuka, Elsa M. ^[4] ; Martins, Joilson O. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Paulista, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci FCF, Dept Clin & Toxicol Anal, Lab Immunoendocrinol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Bioquim, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci FCF, Dept Clin & Toxicol Anal, Lab Microbiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 9, JAN 17 2019.
• Citações Web of Science: 0

Resumo

Introduction: Staphylococcus aureus may provoke peritonitis and death, especially in immunocompromized individuals such as diabetic patients. We evaluated the role of insulin in S. aureus-induced peritoneal infection in diabetic and non-diabetic rats. Materials/Methods: Alloxan-diabetic male Wistar rats and their respective controls received intraperitoneal injections of different strains of S. aureus or sterile phosphate-buffered saline. After 3 days of infection, the first set of diabetic and non-diabetic rats received 4 and 1 IU, respectively, of neutral protamine Hagedorn insulin and were analyzed 8 h later. The second set of diabetic and non-diabetic rats received 4 and 1 IU, respectively, of insulin 2 h before intraperitoneal infection and a half dose of insulin at 5 p.m. for the next 2 days and were analyzed 16 h later. The following measurements were performed: (a) number of cells in the peritoneal lavage fluid (PeLF), white blood cell count, and blood glucose; (b) serum insulin and corticosterone; (c) cytokine levels in the PeLF; (d) expression of adhesion molecules in the vascular endothelium; and (e) microbicidal activity. Results: Diabetic rats showed an increased number of polymorphonuclear leukocytes (PMNs) and increased concentrations of CINC-1, IL-4, and IFN-gamma in the PeLF after infection with the ATCC 25923 or N315 alpha HL+ strain. The mesenteric expression of PECAM-1 was increased after infection with the N315 HLA(+) strain. ICAM-1 expression was increased with ATCC infection. Treatment of diabetic rats with a single dose of insulin restored CINC-1 levels in the PeLF for both strains; however, PMN migration, IL-4, and IFN-gamma were restored in rats infected with the ATCC strain, whereas the PeLF concentrations of CINC-2, IL-1 beta, and IL-4 were increased in N315-infected animals. Insulin restored PMN migration and CINC-2 levels in the PeLF in ATCC-infected rats. After multiple treatments with insulin, the levels of IL-1 beta, IL-6, and IFN-gamma were increased in the PeLF of diabetic rats after infection with either strain, and CINC-2 levels were restored in N315-infected animals. Conclusion: These results suggest that insulin distinctively modulates cytokine production or release, PMN leukocyte migration, and adhesion molecule expression during the course of peritonitis induced by different strains of S. aureus. (AU)

• Processo FAPESP: 14/05214-1 - Investigando o papel da insulina em diferentes infecções em animais diabéticos e sadios
• Beneficiário: Joilson de Oliveira Martins
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/06652-7 - Aspectos celulares e moleculares envolvidos na resposta inflamatória induzida pela carragenina em camundongos sadios e diabéticos
• Beneficiário: Fernanda Peixoto Barbosa Nunes
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/11540-7 - Investigando o papel da insulina na vigência da inflamação alérgica pulmonar em camundongos diabéticos e sadios
• Beneficiário: Joilson de Oliveira Martins
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/02272-0 - Efeito da insulina na inflamação pulmonar secundária a sepse, na imunidade inata, na ativação do seu gene (BGK) e seus receptores (IR-A e IR-B)
• Beneficiário: Joilson de Oliveira Martins
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores