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The role of MMP2 in persistent inflammation in Chronic Obstructive Pulmonary Disease (COPD)
Author(s) -
Gosselink John,
Hayashi Shizu,
Elliott W Mark,
Xing Li,
Chan Becky,
Wright Claire,
Pare Peter,
Sin Don,
Pierce John,
Pierce Richard,
Patterson Alex,
Cooper Joel,
Hogg James
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.572.13
Subject(s) - mmp2 , copd , medicine , chemokine , inflammation , chemokine receptor , biomarker , lung , pathology , immunology , biology , cancer , metastasis , biochemistry
Rationale MMP2 modifies chemokines in ways that allow them to continue to bind to their receptors but fail to activate them (Science. 2000, 289:1202‐6). Objective To investigate the role of MMP2 expression and activity in the development of the persistent inflammatory process associated with progression of COPD. Methods The expression of MMP2 was measured by Taqman quantitative PCR in 136 paired samples of small bronchioles and surrounding lung tissue separated by laser capture microdissection from 63 patients in all 4 categories of COPD severity. MMP2 mRNA expression was compared to forced expiratory volume in one second (FEV 1 ) by linear regression analysis. As well, MMP2 activity was measured in 11 of these COPD patients' lungs by gelatin zymography. Results MMP2 expression and activity decreased in both the small airways and surrounding lung tissue with disease progression in COPD. Conclusions This sharp reduction of MMP2 expression and activity may contribute to the persistence of the inflammatory process in COPD by reducing the proteolytic modification of chemokines that normally blocks chemokine receptors to reduce the inflammatory response. Supported by grants NIH‐HL‐P50 084922 and CIHR MOP‐82815