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Hsp90 regulation affects the treatment of glucocorticoid for pancreatitis-induced lung injury
- Source :
- Molecular and cellular biochemistry. 440(1-2)
- Publication Year :
- 2017
-
Abstract
- Glucocorticoids are commonly used for the treatment of pancreatitis and complicated acute lung injury and help to reduce the mortality rates of both. The effect of gene variants in heat shock protein 90 (Hsp90), a key chaperone molecule of the glucocorticoid receptor (GR), on the therapeutic effect of glucocorticoids is unclear. Our study aims to investigate the different susceptibility to glucocorticoid treatment in BALB/c and C57BL/6 mice carrying different Hsp90 genotypes in an animal model of pancreatitis-induced lung injury. Compared with BALB/c mice, C57BL/6 mice have lower mortality rates, decreased water content in their lungs, and a lower level of IL-1 beta in an animal model of acute pancreatitis. C57BL/6 mice show a greater therapeutic effect and increased GR binding activities with glucocorticoid responsive element compared to BALB/c mice after a 0.4 mg/kg dexamethasone (DEX) treatment. Treatment with a higher dose of DEX (4 mg/kg) significantly reduced mortality rates and increased GR-GRE binding activity in both strains of mice, and there was no significant difference between the two strains. DEX did not exert a protective role after geldanamycin, a specific inhibitor of Hsp90, was administered in both strains of mice. Our study revealed that Hsp90 gene variants are responsible for the greater therapeutic effect of DEX in C57BL/6 mice compared to BALB/c mice, which implies that combining DEX treatment with Hsp90 regulation would promote the efficiency of DEX and would be an effective way to alleviate the side effects of hormone therapy.
- Subjects :
- Male
medicine.medical_specialty
Clinical Biochemistry
Interleukin-1beta
Lung injury
Dexamethasone
03 medical and health sciences
Mice
0302 clinical medicine
Glucocorticoid receptor
Receptors, Glucocorticoid
Heat shock protein
Internal medicine
polycyclic compounds
medicine
Animals
HSP90 Heat-Shock Proteins
Molecular Biology
Lung
Mice, Inbred BALB C
biology
business.industry
Therapeutic effect
Cell Biology
General Medicine
Lung Injury
medicine.disease
Hsp90
Endocrinology
Pancreatitis
030220 oncology & carcinogenesis
biology.protein
030211 gastroenterology & hepatology
business
hormones, hormone substitutes, and hormone antagonists
Glucocorticoid
medicine.drug
Subjects
Details
- ISSN :
- 15734919
- Volume :
- 440
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular biochemistry
- Accession number :
- edsair.doi.dedup.....181f634b30f95d260436ebd1683e5163