Glucocorticoid resistance in COPD patients and lung cancer

Almusrati, WKS

Abstract

COPD is linked to inflammatory mediators that orchestrate the disease progression, mainly in the small airways and in parenchymal tissue. Inflammatory mediators, such as cytokines, chemokines and oxygen free radicals, orchestrate the inflammatory response, causing disruption of the epithelial surface and the surrounding microenvironment in the lung tissue. Glucocorticoids are the main treatment for many inflammatory diseases, however, the majority of COPD patients are resistant to glucocorticoids, so a better understanding of the exact mechanism of glucocorticoid resistance in COPD patients and lung cancer is necessary in order to improve the effectiveness of steroids. Glucocorticoids act through glucocorticoid receptors that are located in the cytoplasm. GRs are phosphorylated, and this post-translational modification affects their binding and interaction with other proteins. In this thesis, the expression of TTC-5, a stress-responsive co-factor, and the total and the phosphorylated GR in the peripheral lung tissue of COPD patients were examined and compared with the expression in healthy patients. Results indicate that total GR and GR phosphorylated at S211 and S226 are expressed in A549 lung cancer cells as well as TTC5. Preliminary results also suggest that TTC5 and GR interact in these cells. Furthermore, as determined by immunohistochemistry, the total GR, GR phosphorylated on S211 and S226 as well as TTC5 are expressed in human lung tissues and in associated macrophages. Finally, we detected altered TTC5 expression that correlates with disease status. These results may contribute to our understanding of the underlying mechanisms of glucocorticoid resistance in COPD and in lung cancer.

Citation

Almusrati, W. (in press). Glucocorticoid resistance in COPD patients and lung cancer. (Dissertation). University of Salford

• Thesis Type: Dissertation
• Acceptance Date: Mar 19, 2023
• Deposit Date: Feb 22, 2016
• Publicly Available Date: Feb 22, 2016
• Additional Information: Funders : Libyan embassy; Projects : LGE 131
• Award Date: Jan 1, 2015