Interleukin 1alpha and interleukin 6 protect human neuronal SH-SY5Y cells from oxidative damage.
Interleukin (IL)-1alpha and IL-6 are powerful inflammatory cytokines produced in brain primarily by microglia and astrocytes. Here we demonstrate, using an in vitro assay system, that they can have a direct neuroprotective action against oxidative attack. Exposure of retinoic acid-differentiated human SH-SY5Y neuroblastoma cells to 270 microM hydrogen peroxide caused activation of caspase 3 and significant neuronal death. Treatment with IL-1alpha or IL-6 caused a dose-dependent increase in survival as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. An antibody against single-strand DNA demonstrated many apoptotic neuroblastoma cells following exposure to hydrogen peroxide, with a decrease following cytokine treatment. These data indicate that IL-1alpha and IL-6 can, under appropriate circumstances, protect neurons from oxidative damage in addition to their well-known action of stimulating inflammation.
Bissonnette
Christopher J
CJ
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada.
Klegeris
Andis
A
McGeer
Patrick L
PL
McGeer
Edith G
EG
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D004277:DNA, Single-Stranded / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D006861:Hydrogen Peroxide; D007375:Interleukin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000494:pharmacology* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
D004277:DNA, Single-Stranded; D007375:Interleukin-1; D015850:Interleukin-6; D018696:Neuroprotective Agents; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases