| title: | The role of cysteinyl leukotrienes and their receptors in the inflammatory remodeling of the human airways – putative mechanisms and targets for pharmacotherapy |
|---|---|
| reg no: | ETF6566 |
| project type: | Estonian Science Foundation research grant |
| subject: |
1.8. Molecular Biology 3.1. Basic Medicine |
| status: | accepted |
| institution: | TU Faculty of Medicine |
| head of project: | Alan Altraja |
| duration: | 01.01.2006 - 31.12.2009 |
| description: | Cysteinyl leukotrienes (CysLTs) C4, D4, and E4 (LTC4, LTD4, and LTE4) are potent lipid mediators, traditionally viewed as potent bronchoconstrictors, are also implicated in chronic airway inflammation and remodeling, a hallmark of asthma and chronic obstructive pulmonary disease (COPD). CysLTs contribute to the remodeling not only through their diverse roles in inflammation but also by their direct effects on airway structural cells. CysLTs act through at least two G-protein-coupled receptors (CysLTR1 and CysLTR2), however, theoretically, there exist diverse possibilities for, but little is known about the role of CysLTs and their receptors in the inflammatory remodeling of the human airways. In this project, we aim at clarifying using the airway structural cells (epithelial cells, fibroblasts, and smooth muscle cells) in vitro: 1) the presence and localization of the CysLT receptors in the cells, both commercial and isolated from patients with asthma and COPD, and from healthy control individuals, as well as the differences between asthma, COPD, and healthy controls for the level of expression of the CysLT receptors, 2) the impact of remodeling-associated growth factors TGF-b, IFN-g, and TNF-a on the expression and cellular localization of the CysLT receptors, 3) which CysLT receptors are involved in mediating the synthesis and secretion of extracellular matrix (ECM) proteins tenascin and laminin b2 chain, 4) by using proteomic approach the effect of CysLT receptor antagonists on the protein pattern of the CysLT-treated cells, and 5) the perspectives of pharmacological inhibition of the ECM protein synthesis and remodeling. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Alan Altraja | Tartu Ülikool | ||
| 2. | Siiri Altraja | |||