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Regulation of matrix metalloproteinase‐9 release from IL‐8‐stimulated human neutrophils
Author(s) -
Chakrabarti Subhadeep,
Patel Kamala D.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1004612
Subject(s) - microbiology and biotechnology , cxc chemokine receptors , kinase , signal transduction , protein kinase c , biology , matrix metalloproteinase , chemokine , mapk/erk pathway , proto oncogene tyrosine protein kinase src , p38 mitogen activated protein kinases , mitogen activated protein kinase , chemokine receptor , receptor , biochemistry
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.