2006年9月
Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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- 巻
- 20
- 号
- 11
- 開始ページ
- 1785
- 終了ページ
- 92
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1096/fj.06-5809com
- 出版者・発行元
- FEDERATION AMER SOC EXP BIOL
Leukotrienes (LTs) and lipoxins (LXs) are lipid mediators that play a key role in regulating acute inflammatory responses. Their roles in neural stem cell (NSC) functions are of interest. We showed here that LTB(4) and LXA(4) regulated proliferation and differentiation of murine NSCs that were isolated from embryo brains. Proliferation of NSCs was stimulated by LTB(4) (3 to 100 nM) and blocked by receptor antagonist (IC(50)=2.7 microM). In contrast, LXA(4), and its aspirin-triggered-15-epi-LXA(4) stable analog attenuated growth of NSCs at as little as 1 nM. Both lipoxygenase (LOX) inhibitors and LTB(4) receptor antagonists caused apoptosis and cell death. Gene chip analysis revealed that growth-related gene expressions such as epidermal growth factor (EGF) receptor, cyclin E, p27, and caspase 8 were tightly regulated by LTB(4); LXA(4) gave the opposite gene expressions. In addition to proliferation, LTB(4) induced differentiation of NSCs into neurons as monitored by neurite outgrowth and MAP2 expression. These results indicate for the first time that LTB(4) and LXA(4) directly regulate proliferation and differentiation of NSCs, suggesting these new pathways may be useful in restoring stem cells.
- リンク情報
- ID情報
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- DOI : 10.1096/fj.06-5809com
- ISSN : 0892-6638
- eISSN : 1530-6860
- PubMed ID : 16940150
- Web of Science ID : WOS:000240267000006