Glucocorticoid receptor and heat shock protein 90 in peripheral blood mononuclear cells from asthmatics.
OBJECTIVE
To investigate the expression of glucocorticoid receptor (GR) and heat shock protein 90 (HSP90) mRNA in peripheral blood mononuclear cells (PBMCs) from steroid-sensitive (SS), steroid-dependent (SD) and steroid-resistant (SR) asthmatics patients, and to evaluate the role of GR and HSP90 in the pathogenesis of SR.


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expressions of GR and HSP90 mRNA in PBMC stimulated with IL-2 and/or IL-4 from 10 normal volunteers, 10 SS, 5 SD and 6 SR patients.


RESULTS
The expressions of GR and HSP90 mRNA were the highest in PBMC from SR patients (0.730 +/- 0.171 and 1.122 +/- 0.165, respectively) compared with the normals (P < 0.05). The second was from SS patients (0.359 +/- 0.350 and 0.885 +/- 0.250, respectively). The lowest was from the SD patients (0.017 +/- 0.008 and 0.078 +/- 0.039, respectively). The ratio of HSP90/GR in SR was significantly lower than that in the others, and it suggested that the expression of HSP90 mRNA was not sufficient in this group of patients. When PBMC from SS, SD and SR was incubated with IL-2 or IL-4 alone, no changes in GR and HSP90 mRNA expression were observed. While incubated with combination of IL-2 and IL-4, a significantly higher expression of GR mRNA was observed in all asthmatics, and a significantly higher expression of HSP90 mRNA was observed only in SS and SD patients.


CONCLUSIONS
The lowering of HSP90/GR ratio may be one of the causes of SR. IL-2 and IL-4 may play roles in the imbalance of HSP90/GR.
Qian
X
X
Department of Respiratory Disease, Peking Union Medical College Hospital, Beijing 100730, China.
Zhu
Y
Y
Xu
W
W
Lin
Y
Y
D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D004351:Drug Resistance; D005938:Glucocorticoids / Q000627:therapeutic use; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics*
D005938:Glucocorticoids; D018841:HSP90 Heat-Shock Proteins; D007376:Interleukin-2; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015847:Interleukin-4