Proinflammatory cytokines and apoptosis following glutamate-induced excitotoxicity mediated by p38 MAPK in the hippocampus of neonatal rats.
The proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 rise during neuronal damage and activate the apoptotic mitogen-activated protein kinase p38. We studied apoptosis, the levels of TNF-alpha, IL-1beta, and IL-6, and the cell type producing TNF-alpha in rats at 8, 10, and 14 days of age after neonatal exposure to glutamate, which induces neuronal damage. TNF-alpha production was significantly increased by glutamate, but inhibited by SB203580 (a p38 inhibitor). TNF-alpha, IL-1beta, and IL-6 mRNA levels increased, but SB203580 did not modify their expression. Thus, the p38 signaling pathway influences the expression of inflammatory genes and its inhibition may offer anti-inflammatory therapy.
Chaparro-Huerta
V
V
Laboratorio de Neurobiología Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, México.
Rivera-Cervantes
M C
MC
Flores-Soto
M E
ME
Gómez-Pinedo
U
U
Beas-Zárate
C
C
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007093:Imidazoles / Q000008:administration & dosage; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D012970:Sodium Glutamate / Q000008:administration & dosage / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D016207:Cytokines; D007093:Imidazoles; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D012970:Sodium Glutamate