Emergence of a metalloproteinase/phospholipase A2 axis of systemic inflammation
| Autor: | Dickson Leung, Carlos Fernandez-Patron |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0303 health sciences
Metalloproteinase Chemokine biology business.industry Inflammation 030204 cardiovascular system & hematology Matrix metalloproteinase Systemic inflammation Metalloproteinases In Medicine Article 3. Good health Cell biology Extracellular matrix 03 medical and health sciences 0302 clinical medicine Phospholipase A2 Immunology biology.protein medicine medicine.symptom Prostaglandin E2 business 030304 developmental biology medicine.drug |
| Zdroj: | Metalloproteinases In Medicine. |
| ISSN: | 2324-2027 |
| Popis: | Carlos Fernandez-Patron,1 Dickson Leung2 1Department of Biochemistry, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada, 2Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada Abstract: We review select aspects of the biology of matrix metalloproteinases (MMPs) with a focus on the modulation of inflammatory responses by MMP-2. MMP-2 is a zinc- and calcium-dependent endoprotease with substrates including extracellular matrix proteins, vasoactive peptides, and chemokines. Humans and mice with MMP-2 deficiency exhibit a predominantly inflammatory phenotype. Recent research shows that MMP-2 deficient mice display elevated activity of a secreted phospholipase A2 in the heart. Additionally, MMP-2 deficient mice exhibit abnormally high prostaglandin E2 levels in various organs (ie, the heart, brain and liver), signs of inflammation and exacerbated lipopolysaccharide-induced fever. We briefly review the biology of sPLA2 enzymes to propose the existence of a heart-centric MMP-2/sPLA2 axis of systemic inflammation. Moreover, we postulate that PLA2 activation is induced by chemokines, whose ability to signal inflammation is regulated in a tissue-specific fashion by MMPs. Thus, genetic and pharmacologically induced MMP deficiencies can be expected to perturb PLA2-mediated inflammatory mechanisms. Keywords: MMPs, inflammation, chemokines, secreted phospholipase A2 |
| Databáze: | OpenAIRE |
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