[The influence of dexamethasone on mRNA expression of interleukin-5, interleukin-3 and granulocyte-macrophage colony-stimulating factor receptors in eosinophils of guinea pig asthma model].
OBJECTIVE
To investigate the iufluence of dexamethasone (DM) on expression of interleukin-5 receptor alpha(IL-5R alpha), interleukin-3 receptor alpha (IL-3R alpha), granulocyte-macrophage-colony-stimulating factor receptor alpha(GM-CSFR alpha) and common beta receptor (beta cR) in bronchalveolar lavage fluid (BALF) eosinophils in guinea pig asthma model, and to study the mechanism of promotion effect of steroid on eosinophil apoptosis.


METHODS
18 guinea pigs were divided into three groups randomly, normal control group, asthma group and DM-treated group. Asthma models of guinea pig were sensitized by ovalbumin(OVA). Hypodense EOS (HEOS) and normodense EOS (NEOS) were purified from BALF by gradients of percoll. Apoptosis was detected by method of TdT-mediated dUTP nick end labeling. The mRNA expression of IL-5R alpha, IL-3R alpha, GM-CSFR alpha and common beta receptor (beta cR) in eosinophils were measured by RT-PCR and in situ hybridization.


RESULTS
Apoptosis of HEOS and NEOS in asthma group(4.0 +/- 2.0 and 3.0 +/- 2.0, respectively) were significanteylower than normal group(8.0 +/- 2.0 and, 7.0 +/- 2.0 respectively, P < 0.01), while the numbers of EOS cells (75.2 +/- 12.6 and 50.7 +/- 11.2, respectively) were significantly higher than normal group (4.8 +/- 1.5 and 9.5 +/- 2.6, respectively, P < 0.01). The BALF HEOS and NEOS of asthma group were remarkably reduced after DM treatment (14.8 +/- 8.0 and 20.0 +/- 7.0, respectively, P < 0.01), Eosinophils apoptosis in DM-treated group (24.0 +/- 5.0 and 22.0 +/- 4.0, respectively) was remarkably higher than those in asthma group (P < 0.01); The expressions of IL-5R alpha, IL-3R alpha, GM-CSFR alpha mRNA of BALF EOS of asthma group were significantly lower, but the expression of beta cR mRNA was significantly higher than those of normal group(P < 0.01, 0.05). The expressions of IL-5R alpha, IL-3R alpha, GM-CSFR alpha mRNA in EOS of DM-treated group were significantly higher, while the expression of beta cR mRNA were significantly lower than those of asthma group (P < 0.01, 0.05).


CONCLUSIONS
DM promote the apoptosis of BALF EOS of guinea pigs asthma models. and reduce EOS infiltration in lung of guinea pigs asthma models. It also decreased the effect of IL-5, IL-3 and GM-CSF and promoted the apoptosis of lung EOS through inducing the mRNA expression of their specific alpha chain and reducing the mRNA expression of the common beta chain.
Li
Z
Z
Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Wang
C
C
Qian
G
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D016185:Receptors, Interleukin-3 / Q000235:genetics; D053649:Receptors, Interleukin-5; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D053649:Receptors, Interleukin-5; D003907:Dexamethasone