F-spondin plays a critical role in murine neuroblastoma survival by maintaining IL-6 expression.
F-spondin is associated with the regulation of axonal growth and the development of the nervous system. Its mechanism of action, however, is not clearly understood. In this study, we found that murine neuroblastoma Neuro-2a cells expressed a significant level of IL-6, but only trace amounts of IL-12, tumor necrosis factor alpha and nitric oxide. Knock-down of F-spondin mRNA in murine neuroblastoma NB41A3 and Neuro-2a cells using small interfering RNAs led to decreased IL-6 levels along with lower resistance to serum starvation and cytotoxic amyloid beta(1-42) (Abeta(1-42)) peptide. Restoring decline of F-spondin or IL-6 induced by F-spondin knock-down through adding exogenous F-spondin, IL-6 or over-expressing F-spondin reversed the cell death induced by Abeta(1-42) peptide or serum starvation. The decrease of IL-6 level was positively correlated with decrease of NF-kappaB and inhibition of p38 mitogen-activated protein kinase (MAPK). Over-expressing MEKK, a kinase activator of the p38 MAPK pathway, increased IL-6 production, restored the decrease of p38 induced by F-spondin knock-down, and rescued the cells from death caused by Abeta(1-42) peptide. Taken together, these results suggest that F-spondin may play a critical role in murine neuroblastoma survival under adverse conditions by maintaining IL-6 level via a MEKK/p38 MAPK/NF-kappaB-dependent pathway.
Cheng
Yung-Chih
YC
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
Liang
Chi-Ming
CM
Chen
Yen-Po
YP
Tsai
Inn-Ho
IH
Kuo
Cheng-Chin
CC
Liang
Shu-Mei
SM
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D016326:Extracellular Matrix Proteins; D015850:Interleukin-6; D016328:NF-kappa B; C429104:SPON1 protein, human; D048051:p38 Mitogen-Activated Protein Kinases