Changes of 5-lipoxygenase pathway and proinflammatory mediators in cerebral cortex and lung tissue of sensitized rats.
OBJECTIVE
To explore the change of 5-lipoxygenase (5-LO) pathway expression and proinflammatory mediators level of lung tissue and cerebral cortex, and the possible regulatory mechanism through central nervous 5-LO pathways to pulmonary inflammatory status in antigen repeated challenged rats.


METHODS
Four groups of rats were treated as control, asthma model, asthma model treatment with dexamethasone (DXM, 0.5 mg/kg, i.p.) and ketotifen (5 mg/kg, i.g.). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, interferon (IFN)-gamma, and nitric oxide (NO) were detected by ELISA kits. The mRNA expression of 5-LO and LTA4-hydrolase (LTA4-H) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), and the protein content of 5-LO was measured by Western blot.


RESULTS
Increase of TNF-alpha, IL-4, NO level, and decrease of IFN-gamma level in bronchoalveolar lavage fluid (BALF) and cerebral cortex in sensitized rats were shown after repeated antigen challenge. The expression of 5-LO and LTA4-H mRNA, and 5-LO protein levels were increased in lung tissue and cerebral cortex in asthma rats. In comparison with the asthma model, DXM significantly inhibited the increase of cytokine levels and the expression of 5-LO pathway enzyme (P<0.05). Ketotifen also inhibited the increase of TNF-alpha level and 5-LO pathway enzyme expression in lung and cerebral cortex, but had no effect on the level of NO, IL-4, and IFN-gamma.


CONCLUSIONS
The correlative increase of 5-LO pathway enzyme expression and proinflammatory mediators of brain may have a regulatory effect on pulmonary inflammation in asthma.
Deng
Yang-mei
YM
Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of China, Medical School of Zhejiang University, Hangzhou 310031, China.
Xie
Qiang-min
QM
Zhang
Shui-juan
SJ
Chen
Ji-qiang
JQ
Yang
Qiu-huo
QH
Bian
Ru-lian
RL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000201:enzymology* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D006634:Histamine H1 Antagonists; D012333:RNA, Messenger; D003907:Dexamethasone; D001094:Arachidonate 5-Lipoxygenase; D007665:Ketotifen