[Glucocorticoid receptor and HSP 90 mRNA expression in peripheral blood mononuclear cell from steroid resistant asthmatics].
OBJECTIVE
To investigate the expression of glucocorticoid receptor (GR) and HSP 90 mRNA in peripheral blood mononuclear cells (PBMC) from steroid-sensitive asthma (SS), steroid-dependant asthma (SD) and steroid-resistant asthma (SR) and assess the role of GR and HSP 90 in the pathogenesis of SR.


METHODS
With reverse transcription-polymerase chain reaction (RT-PCR), expression of GR and HSP 90 mRNA were detected in PBMC without or with IL-2 and (or) IL-4 stimulation from 10 normal volunteers, 10 SS, 5 SD and 6 SR patients.


RESULTS
Expression of GR and HSP 90 mRNA in PBMC was the highest in SR group (0.730 +/- 0.171, 1.122 +/- 0.165 respectively), then in SS group (0.359 +/- 0.350, 0.885 +/- 0.250 respectively), the lowest in SD group (0.017 +/- 0.008, 0.078 +/- 0.039 respectively). The expression of GR and HSP 90 mRNA in PBMC from normal volunteers was 0.052 +/- 0.013 and 0.362 +/- 0.101 respectively. The difference of the expression of GR or HSP 90 was significant between each group (P < 0.05). The ratio of HSP 90/GR in normal volunteers, SS, SD and SR patients was 7.15 +/- 1.84, 8.39 +/- 7.95, 5.51 +/- 3.30 and 1.57 +/- 0.18 respectively. HSP 90/GR in SR was significant lower than those of the others, suggesting that the expression of HSP 90 mRNA was in sufficient in this group. When PBMC were incubated with combination of IL-2 and IL-4, a significant higher over expression of GR mRNA was observed in all asthmatic group and a significant higher expression of HSP 90 mRNA was observed only in SS and SD groups but not in SR group.


CONCLUSIONS
The low expression of HSP 90 mRNA and the lowering ratio of HSP 90/GR mRNA may be related to the pathogenesis of SR. Different response to IL-2 and IL-4 may play a role in the development of HSP 90/GR imbalance.
Qian
X
X
Department of Respiratory Disease, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Zhu
Y
Y
Xu
W
W
D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D013256:Steroids / Q000494:pharmacology
D018841:HSP90 Heat-Shock Proteins; D007376:Interleukin-2; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D013256:Steroids; D015847:Interleukin-4