Proteomics: is it an approach to understand the progression of chronic lung disorders?
Tissue injury, mediated by pathologically elevated production and action of various serine- and matrix metalloproteinases (MMPs), is a hallmark of chronic inflammatory airway diseases (CIAD). CIAD includes such diseases as bronchial asthma, bronchiectasis, and chronic obstructive pulmonary disease. Tissue injury, as a consequence of chronic inflammation, can disturb the relevant repair mechanisms and also result in irreversible alteration of lung architecture. By use of proteomic methods, we analyzed proteinase cascades as an initiator of tissue destruction in CIAD. The present results revealed that elevated levels of MMP-8, -13, -14, and -2, mainly in active forms, can also be detected in CIAD BALFs. Enhanced levels of different active MMPs evidently reflect ongoing tissue-destructive inflammation and airway remodeling occurring in CIAD lung. An inverse correlation between BALF MMP-8 levels and activation degree and airflow obstruction in bronchial asthma tissue injury was shown for the first time. This strongly indicates that chronic peri-inflammatory tissue injury is a main cause of decline of lung functional capacity. Together, these data suggest that the serine and MMP proteinase network is an important feature in predicting clinical worsening of airway obstruction in CIAD. Activation of elevated MMPs seems to have a common profile for all studied CIAD, but different lung disorders react differently to ICS treatment.
Sepper
Ruth
R
North-Estonia Regional Hospital, Sütiste 19, 13419 Tallinn, Estonia.
Prikk
Kaiu
K
D001249:Asthma / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D002908:Chronic Disease; D017364:Collagenases / Q000096:biosynthesis; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008171:Lung Diseases / Q000175:diagnosis* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020784:Matrix Metalloproteinase 8 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis; D008954:Models, Biological; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D013379:Substrate Specificity
D020543:Proteome; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8