Published online before print April 14, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Article |
@
Departments of *Physiology and Biophysics and Biochemistry and Molecular Biology, Immunology Research Group, University of Calgary, Alberta, Canada
@ To whom correspondence should be addressed. E-mail: kpatel{at}ucalgary.ca.
Matrix metalloproteinase-9 (MMP-9) is present in the tertiary granules of neutrophils and can be released following stimulation. We examined the signaling mechanisms that regulate interleukin-8 (IL-8)-mediated MMP-9 release from neutrophils. IL-8 activates neutrophils by interacting with two receptors: CXC chemokine receptor 1 (CXCR1) and CXCR2. Blocking CXCR1 had no effect on IL-8-mediated MMP-9 release, whereas blocking CXCR2 significantly reduced MMP-9 release. We also found that stimulating CXCR2 alone was sufficient to induce MMP-9 release. This process was independent of changes in the intracellular calcium concentration. Src-family kinases and protein kinase C (PKC) were involved in two mutually exclusive pathways regulating IL-8-mediated MMP-9 release. Inhibition of extracellular signal-regulated kinase (ERK)1/2 blocked IL-8-mediated MMP-9 release; however, inhibition of p38 mitogen-activated protein kinase had no effect on MMP-9 release. We found ERK1/2 was activated downstream of PKC but not Src-family kinases in this system. These data suggest that IL-8-induced MMP-9 release from neutrophils is mediated through CXCR2 and involves two distinct pathways, one involving PKC and ERK1/2 and the other involving Src-family kinases. Furthermore, our data show that the mechanisms that regulate MMP-9 release from tertiary granules are different from those that regulate primary granule release.
Key Words: signal transduction • tissue remodeling • chemokines • inflammation
This article has been cited by other articles:
 |
|
 |
|
  P. Ehrenfeld, C. E. Matus, F. Pavicic, C. Toledo, F. Nualart, C. B. Gonzalez, R. A. Burgos, K. D. Bhoola, and C. D. Figueroa Kinin B1 receptor activation turns on exocytosis of matrix metalloprotease-9 and myeloperoxidase in human neutrophils: involvement of mitogen-activated protein kinase family J. Leukoc. Biol., November 1, 2009; 86(5): 1179 - 1189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Page, J. R. Ledford, P. Zhou, and M. Wills-Karp A TLR2 Agonist in German Cockroach Frass Activates MMP-9 Release and Is Protective against Allergic Inflammation in Mice J. Immunol., September 1, 2009; 183(5): 3400 - 3408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhao, J. R. Town, F. Li, X. Zhang, D. W. Cockcroft, and J. R. Gordon ELR-CXC Chemokine Receptor Antagonism Targets Inflammatory Responses at Multiple Levels J. Immunol., March 1, 2009; 182(5): 3213 - 3222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Tan, J. S. Lee, M. L. Manni, C. L. Fattman, J. M. Tobolewski, M. Zheng, J. K. Kolls, T. R. Martin, and T. D. Oury Inflammatory Cells as a Source of Airspace Extracellular Superoxide Dismutase after Pulmonary Injury Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 226 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chakrabarti, J. M. Zee, and K. D. Patel Regulation of matrix metalloproteinase-9 (MMP-9) in TNF-stimulated neutrophils: novel pathways for tertiary granule release J. Leukoc. Biol., January 1, 2006; 79(1): 214 - 222. [Abstract] [Full Text] [PDF]
|
|
