[The effects of heat shock protein 90 and glucocorticoid receptor on apoptosis in T lymphocytes from asthmatic patients].
OBJECTIVE
Using GA (geldanamycine), which specifically binding to HSP90, to induce the imbalance of HSP90/GR in function (low ratio) and analyzing the effect of low HSP90/GR ratio on T lymphocytes apoptosis induced by Dex from asthmatic patients. The expression of HSP90 and GR mRNA of T lymphocytes influenced by Dex and GA was also studied.


METHODS
Peripheral blood T lymphocytes were enriched from 10 asthmatic subjects and 7 healthy volunteers by nylon column. T lymphocytes were cultured in vitro with Dex and / or GA for 72 hours. Apoptosis of T lymphocytes were measured by propidium iodide staining and flowcytometry. With reverse transcription-polymerase chain reaction (RT-PCR), the expression of HSP90 and GR mRNA was detected.


RESULTS
Dex could obviously induce the apoptosis of T lymphocytes from asthmatic patients (33.8% +/- 3.2% vs 23.2% +/- 1.5% , P < 0.01). GA had no effect on the apoptosis of T lymphocytes but could inhibit the effect of Dex (24.5% +/- 6.0% vs 33.8% +/- 3.2% , P < 0.01). Dex also had the effect of inducing apoptosis of T lymphocytes from health volunteers but the effect was less potent than that from asthmatic patients (25.9% +/- 3.5% vs 23.1% +/- 1.5 %, P < 0.05). Dex inhibited the expression of HSP90 and GR mRNA of T lymphocytes from asthmatic patients (1.23 +/- 0.16 vs 1.68 +/- 0.38 and 0.42 +/- 0.06 vs 0.54 +/- 0.07, respectively, P all < 0.05). GA could interrupt the inhibiting effect of Dex on the expression of HSP90 and GR mRNA but had no effect on it.


CONCLUSIONS
The low ratio of HSP90/GR could reduce the inducing apoptosis effect of Dex. Dex could down-regulate the mRNA expression of HSP90 and GR and GA could interrupt the inhibiting effect of Dex.
Qian
X
X
Department of Respiratory Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Bering 100730, China.
Zhu
Y
Y
Xu
W
W
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000473:pathology*
D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid