Leukemia inhibitory factor in the neuroimmune communication pathways in allergic asthma.
In the pathogenesis of asthma, central sensitization is suggested to be an important neural mechanism, and neurotrophins and cytokines are likely to be the major mediators in the neuroimmune communication pathways of asthma. However, their impact on the central nervous system in allergic asthma remains unclear. We hypothesize that central neurogenic inflammation develops in the pathogenesis of allergic asthma, and nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are important mediators in its development. An asthma model of rats was established by sensitization and challenged with ovalbumin (OVA). For further confirmation of the role of LIF in neurogenic inflammation, a subgroup was pretreated with intraperitoneally (i.p.) LIF antibody before OVA challenge. The levels of LIF and NGF were measured with reverse transcription and polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry stain in lung tissue, airway-specific dorsal root ganglia (DRG, C7-T5) and brain stem of asthmatic rats, anti-LIF pretreated rats and controls. A significantly increased number of LIF- and NGF-immunoreactive cells were detected in lung tissue, DRG and the brain stem of asthmatic rats. In the asthma group a significantly increase level of mRNA encoding LIF and NGF in lung tissue was detected, but not in DRG and the brain stem. Pretreatment with LIF antibody decreased the level of LIF and NGF in all tissues. LIF is an important mediator in the crosstalk between nerve and immune systems. Our study demonstrate that the increased level of LIF and NGF in DRG and brain stem may be not based on result from de novo synthesis, but rather on result from retrograde nerve transport or passage across the blood-brain-barrier.
Department of Pulmonology, First Affiliated Hospital, Jinan University, Guangzhou, China. Electronic address: amnlmj94@hotmail.com.
Min-Juan
MJ
Lin
Department of General Surgery, First Affiliated Hospital, Jinan University, Guangzhou, China.
Xue-Jun
XJ
Lao
Department of Pulmonology, First Affiliated Hospital, Jinan University, Guangzhou, China.
Sheng-Ming
SM
Liu
Department of Pulmonology, First Affiliated Hospital, Jinan University, Guangzhou, China.
Zhen-Hua
ZH
Xu
Department of Pulmonology, First Affiliated Hospital, Jinan University, Guangzhou, China.
Wei-Feng
WF
Zou
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D015213:Neuroimmunomodulation; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley
D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; D010047:Ovalbumin; D020932:Nerve Growth Factor
Allergic asthma; Brain stem; Dorsal root ganglia; Leukemia inhibitory factor; Nerve growth factor