Genetic background of chronic obstructive pulmonary disease (COPD); regulation of inflammation in pulmonary epithelial cells through innate immune receptors activity

Glavni istraživač

Kategorija
Znanstveni projekti Ministarstva znanosti, obrazovanja i športa
Datum početka
1.1.2014.
Datum završetka
31.12.2015.
Status
Završen

Zavod za molekularnu medicinu

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder defined as a non-reversible airflow obstruction followed by chronic inflammation of airways.

Cigarette smoke and other noxious particles are the major environmental risk factors for COPD. Environmental risk factors have strong impact on disease development but the fact that only 20% of smokers develop COPD suggest that genetics could play a key role in the pathogenesis and prognosis of disease. Unbalanced inflammation of lungs is associated with diseased conditions.

Pulmonary epithelial and immune cells are equipped with diverse pattern recognition receptors (PRRs) able to initiate appropriate immune response to invading pathogens or tissue damage associated molecules. Toll-like receptors (TLRs) are PRRs with a central function in the induction of immune response via intracellular signaling events involving nuclear factor (NF)-κB, and interferon regulatory factor transcription factors leading to subsequent production of proinflammatory cytokines and type I interferons (IFN). COPD is accompanied with severe exacerbations, the majority of which are associated with viral and bacterial respiratory tract infection, indicating the importance of innate immunity in disease pathogenesis.

Because of global increase in COPD prevalence, strong association with lung cancer and absence of specific therapeutic targets, elucidation of specific gene involvement and how they function in diseased conditions will dramatically improve disease treatment at personalized level.

Therefore, the specific aims of this project could be sub-divided into a two specific work area:

  1. Search for prognostic and diagnostic biomarkers
  2. In vitro analysis of detected biomarkers

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