[Effect of glucocorticoid on neurokinin A in plasma and lungs of guinea pigs with asthma and molecular mechanism of the effect].
OBJECTIVE
Bronchial asthma is a chronic inflammatory disorder of the airways caused by many complicated elements. Recently, a close attention has been paid to the neurogenic inflammation in airways, which is mediated by sensory neuropeptides secreted by sensory nerve. Neurokinin A (NKA) is an important transmitter of non-cholinergic excitatory nerves in the lung which is an important sensory neuropeptide causing airway neurogenic inflammation. The purpose of this study was to investigate the effect of glucocorticoid (dexamethasone) on neurokinin A in plasma and lungs of guinea pigs with asthma and to explore its molecular mechanism.


METHODS
Thirty guinea pigs (1.5 months old and weighed 200 - 225 g) were sensitized by exposure to aerosolized ovalbumin and challenged with the same antigen to establish asthma model. These animals were divided randomly into dexamethasone-treatment group and non-dexamethasone-treatment group (15 guinea pigs in each group). Normal control group animals (n = 15) were treated with normal saline (NS) instead of aerosolized ovalbumin. The guinea pigs in the dexamethasone-treatment group were treated with dexamethasone (5.0 mg/kg, intraperitoneal injection) one day before asthma-inducement, on the day of inducement and 24 h after inducement. The non-dexamethasone-treatment group animals were treated with NS (5.0 mg/kg, intraperitoneal injection) on the same days as the dexamethasone-treatment group was treated. The normal control group animals were treated with NS (5.0 mg/kg, intraperitoneal injection). The contents of NKA in the plasma and lung tissues were detected by ELISA; the expression of NKA mRNA in lung tissues was examined by RT-PCR.


RESULTS
(1) The contents of NKA in the plasma (2.20 +/- 0.46 ng/ml), lung tissues (5.02 +/- 2.11 ng/g x protein) and the NKA mRNA expression in the lung tissues (1.10 +/- 0.06) of guinea pigs with induced asthma were significantly higher than those of the normal control group (plasma 0.84 +/- 0.33 ng/ml, lung tissues 2.56 +/- 0.80 ng/g x protein, mRNA 0.30 +/- 0.04; P < 0.001, respectively). (2) The contents of NKA in the plasma, lung tissues and the NKA mRNA expression in the lung tissues of guinea pigs with induced asthma were significantly lower in dexamethasone-treatment group (plasma 0.98 +/- 0.23 ng/ml, lung tissues 2.71 +/- 0.50 ng/g x protein, mRNA 0.35 +/- 0.07) than those in the non-dexamethasone-treatment group (plasma 2.20 +/- 0.46 ng/ml, lung tissues 5.02 +/- 2.11 ng/g x protein, mRNA 1.10 +/- 0.06; P < 0.001, respectively). No significant difference was found between the dexamethasone-treatment group and the normal control group (P > 0.05, respectively).


CONCLUSIONS
(1) NKA mRNA expression in the lungs of guinea pigs with asthma was up-regulated and NKA contents were higher in plasma and lungs; (2) Glucocorticoid could significantly decrease the contents of NKA in plasma, lung tissues of guinea pigs with induced asthma; the mechanism of the effect may be related to down-regulation of NKA mRNA expression in lung tissues caused by glucocorticoid.
Shang
Yun-xiao
YX
Department of Pediatrics, The Second Affiliated Hospital, China Medical University, Shenyang 110004, China.
Zhang
Han
H
Han
Xiao-hua
XH
Zhao
Shu-qin
SQ
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D015288:Neurokinin A / Q000097:blood / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D015288:Neurokinin A; D010047:Ovalbumin