PMID- 22734808
OWN - NLM
STAT- MEDLINE
DCOM- 20130117
LR  - 20220330
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 9
DP  - 2012 Jun 26
TI  - Transforming growth factor beta1-induced astrocyte migration is mediated in part by 
      activating 5-lipoxygenase and cysteinyl leukotriene receptor 1.
PG  - 145
LID - 10.1186/1742-2094-9-145 [doi]
AB  - BACKGROUND: Transforming growth factor-beta 1 (TGF-beta 1) is an important regulator of 
      cell migration and plays a role in the scarring response in injured brain. It is 
      also reported that 5-lipoxygenase (5-LOX) and its products, cysteinyl 
      leukotrienes (CysLTs, namely LTC(4), LTD(4) and LTE(4)), as well as cysteinyl 
      leukotriene receptor 1 (CysLT(1)R) are closely associated with astrocyte 
      proliferation and glial scar formation after brain injury. However, how these 
      molecules act on astrocyte migration, an initial step of the scarring response, 
      is unknown. To clarify this, we determined the roles of 5-LOX and CysLT(1)R in 
      TGF-beta 1-induced astrocyte migration. METHODS: In primary cultures of rat 
      astrocytes, the effects of TGF-beta 1 and CysLT receptor agonists on migration and 
      proliferation were assayed, and the expression of 5-LOX, CysLT receptors and 
      TGF-beta1 was detected. 5-LOX activation was analyzed by measuring its products 
      (CysLTs) and applying its inhibitor. The role of CysLT(1)R was investigated by 
      applying CysLT receptor antagonists and CysLT(1)R knockdown by small interfering 
      RNA (siRNA). TGF-beta 1 release was assayed as well. RESULTS: TGF-beta 1-induced 
      astrocyte migration was potentiated by LTD(4), but attenuated by the 5-LOX 
      inhibitor zileuton and the CysLT(1)R antagonist montelukast. The non-selective 
      agonist LTD(4) at 0.1 to 10 nM also induced a mild migration; however, the 
      selective agonist N-methyl-LTC(4) and the selective antagonist Bay cysLT2 for 
      CysLT(2)R had no effects. Moreover, CysLT(1)R siRNA inhibited TGF-beta 1- and 
      LTD(4)-induced astrocyte migration by down-regulating the expression of this 
      receptor. However, TGF-beta 1 and LTD4 at various concentrations did not affect 
      astrocyte proliferation 24 h after exposure. On the other hand, TGF-beta 1 increased 
      5-LOX expression and the production of CysLTs, and up-regulated CysLT1R (not 
      CysLT(2)R), while LTD4 and N-methyl-LTC4 did not affect TGF-beta 1 expression and 
      release. CONCLUSIONS: TGF-beta 1-induced astrocyte migration is, at least in part, 
      mediated by enhanced endogenous CysLTs through activating CysLT(1)R. These findings 
      indicate that the interaction between the cytokine TGF-beta 1 and the 
      pro-inflammatory mediators CysLTs in the regulation of astrocyte function is 
      relevant to glial scar formation.
FAU - Huang, Xue-Qin
AU  - Huang XQ
AD  - Department of Pharmacology, Key Laboratory of Medical Neurobiology of Ministry of 
      Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang 
      University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
FAU - Zhang, Xia-Yan
AU  - Zhang XY
FAU - Wang, Xiao-Rong
AU  - Wang XR
FAU - Yu, Shu-Ying
AU  - Yu SY
FAU - Fang, San-Hua
AU  - Fang SH
FAU - Lu, Yun-Bi
AU  - Lu YB
FAU - Zhang, Wei-Ping
AU  - Zhang WP
FAU - Wei, Er-Qing
AU  - Wei EQ
LA  - eng
PT  - Journal Article
DEP - 20120626
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Receptors, Leukotriene)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 73836-78-9 (Leukotriene D4)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - LRF7RW46ID (leukotriene D4 receptor)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Arachidonate 5-Lipoxygenase/*metabolism/physiology
MH  - Astrocytes/cytology/*metabolism
MH  - Cell Movement/*immunology/*physiology
MH  - Enzyme Activation/physiology
MH  - Leukotriene D4/pharmacology
MH  - Primary Cell Culture
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Leukotriene/*metabolism/physiology
MH  - Transforming Growth Factor beta1/pharmacology/*physiology
PMC - PMC3419068
EDAT- 2012/06/28 06:00
MHDA- 2013/01/18 06:00
PMCR- 2012/06/26
CRDT- 2012/06/28 06:00
PHST- 2012/01/14 00:00 [received]
PHST- 2012/05/17 00:00 [accepted]
PHST- 2012/06/28 06:00 [entrez]
PHST- 2012/06/28 06:00 [pubmed]
PHST- 2013/01/18 06:00 [medline]
PHST- 2012/06/26 00:00 [pmc-release]
AID - 1742-2094-9-145 [pii]
AID - 10.1186/1742-2094-9-145 [doi]
PST - epublish
SO  - J Neuroinflammation. 2012 Jun 26;9:145. doi: 10.1186/1742-2094-9-145.