p38 MAP kinase regulates rapid matrix metalloproteinase-9 release from eosinophils

• Published in: Biochemical and biophysical research communications 2004-03, Vol.315 (2), p.463-470
• Main Authors: Wiehler, Shahina, Cuvelier, Susan L, Chakrabarti, Subhadeep, Patel, Kamala D
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Blotting, Western; Cell-Free System - metabolism; Degranulation; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Eosinophils - enzymology; Eosinophils - metabolism; fMLP; Granulocytes; Humans; Inflammation; Leukocytes - metabolism; MAP Kinase Signaling System; MAP kinases; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase 9 - chemistry; Matrix Metalloproteinase 9 - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; N-Formylmethionine Leucyl-Phenylalanine - metabolism; Neutrophils - metabolism; p38 Mitogen-Activated Protein Kinases; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Signal Transduction; Time Factors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.01.078

Eosinophils constitutively produce and store matrix metalloproteinase-9 (MMP-9), a protease implicated in tissue remodeling observed in asthma. In this study, we examined the rapid release of stored MMP-9 from eosinophils following stimulation with either tumor necrosis factor-α (TNF-α) or the bacterial product fMLP. TNF-α induced rapid and robust pro-MMP-9 release from eosinophils. MMP-9 could be detected in the cell-free supernatant as early as 15 min after stimulation. Rapid MMP-9 release was similarly induced by fMLP. TNF-α stimulation activated the mitogen-activated protein (MAP) kinases p38 MAP kinase and extracellular signal-regulated kinase-2 (Erk-2) at times and concentrations similar to that observed for MMP-9 release. Using pharmacological inhibitors, we found that TNF-α-stimulated MMP-9 release was mediated by p38 MAP kinase, but not Erk-1/2. Signaling through p38 MAP kinase may represent a universal mechanism for MMP-9 release from eosinophils, as fMLP-induced MMP-9 release was also regulated by p38 MAP kinase.