Changes of 5-lipoxygenase pathway and proinflammatory mediators in cerebral cortex and lung tissue of sensitized rats
Abstract
Aim: 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, ip) and ketotifen (5 mg/kg, ig). Tumor
necrosis factor (TNF)-α, interleukin (IL)-4, interferon (IFN)-γ, 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-α, IL-4, NO level, and decrease of IFN-γ 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-α 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-γ. Conclusion: The correlative increase of 5-LO pathway
enzyme expression and proinflammatory mediators of brain may have a regulatory
effect on pulmonary inflammation in asthma.
Keywords:
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, ip) and ketotifen (5 mg/kg, ig). Tumor
necrosis factor (TNF)-α, interleukin (IL)-4, interferon (IFN)-γ, 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-α, IL-4, NO level, and decrease of IFN-γ 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-α 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-γ. Conclusion: The correlative increase of 5-LO pathway
enzyme expression and proinflammatory mediators of brain may have a regulatory
effect on pulmonary inflammation in asthma.