Ganglioside GM1 effects on the expression of nerve growth factor (NGF), Trk-A receptor, proinflammatory cytokines and on autoimmune diabetes onset in non-obese diabetic (NOD) mice.
NOD (non-obese diabetic) mice develop type 1 diabetes mellitus spontaneously and with a strong similarity to the human disease. Differentiation and function of pancreas beta cells are regulated by a variety of hormones and growth factors, including the nerve growth factor (NGF). Gangliosides have multiple immunomodulatory activities with immunosuppressive properties, decreasing lymphoproliferative responses and modulating cytokine production. In the present study, serum, pancreas islets and spleen mononuclear cells from NOD mice treated with monosialic ganglioside GM1 (100 mg/kg/day) and the group control which received saline solution were isolated to investigate the proinflammatory cytokines (IL-1beta, IFN-gamma, IL-12, TNF-alpha), NGF and its high-affinity receptor TrkA, peri-islet Schwann cells components (GFAP, S100-beta) expression and the relationship with diabetes onset and morphological aspects. Our results suggest that GM1 administration to female NOD mice beginning at the 4th week of life is able to reduce the index of inflammatory infiltrate and consequently the expression of diabetes, modulating the expression of proinflammatory cytokines (IL-12, IFN-gamma, TNF-alpha and IL-1beta). Furthermore, GM1 increases GFAP, S-100beta and NGF in pancreas islets, factors involved in beta cell survival.
Vieira
Karla Priscila
KP
Laboratório de Imunologia & Alergia Experimental, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), Caixa Postal 6111, Campinas/SP 13081-970, Brazil.
de Almeida e Silva Lima Zollner
Ana Rachel
AR
Malaguti
Carina
C
Vilella
Conceição Aparecida
CA
de Lima Zollner
Ricardo
R
D017668:Age of Onset; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C528900:glial fibrillary astrocytic protein, mouse; D005677:G(M1) Ganglioside; D020932:Nerve Growth Factor; D020917:Receptor, trkA