Premium
F‐spondin plays a critical role in murine neuroblastoma survival by maintaining IL‐6 expression
Author(s) -
Cheng YungChih,
Liang ChiMing,
Chen YenPo,
Tsai InnHo,
Kuo ChengChin,
Liang ShuMei
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06186.x
Subject(s) - p38 mitogen activated protein kinases , neuroblastoma , mapk/erk pathway , microbiology and biotechnology , biology , cancer research , kinase , medicine , endocrinology , cell culture , genetics
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 α 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 β 1–42 (Aβ 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 Aβ 1–42 peptide or serum starvation. The decrease of IL‐6 level was positively correlated with decrease of NF‐κB 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 Aβ 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‐κB‐dependent pathway.