Hypoxia induces epidermal keratinocyte matrix metalloproteinase-9 secretion via the protein kinase C pathway

2007 ◽  
Vol 214 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Edel A. O'Toole ◽  
Rudolf van Koningsveld ◽  
Mei Chen ◽  
David T. Woodley
2002 ◽  
Vol 277 (38) ◽  
pp. 35150-35155 ◽  
Author(s):  
Pierre Olivier Estève ◽  
Éric Chicoine ◽  
Olivier Robledo ◽  
Fawzi Aoudjit ◽  
Albert Descoteaux ◽  
...  

2012 ◽  
Vol 117 (2) ◽  
pp. 293-301 ◽  
Author(s):  
Björn Müller-Edenborn ◽  
Birgit Roth-Z'graggen ◽  
Kamila Bartnicka ◽  
Alain Borgeat ◽  
Alexandra Hoos ◽  
...  

Background Invasion of extracellular matrix is a hallmark of malignant tumors. Clamping maneuvers during cancer surgery reduce blood loss, but trigger reperfusion injury (RI). RI increases cancer recurrence in the reperfused organ through up-regulation of matrix metalloproteinase-9 (MMP-9). Interleukin-8 is an important cytokine in RI promoting accumulation of neutrophils, a major source of MMP-9. Volatile anesthetics were demonstrated to reduce RI. We hypothesized that these anesthetics might attenuate MMP-9 up-regulation and consequently tumor cell invasion in RI. Methods Isolated human neutrophils (n = 6) were preconditioned with sevoflurane or desflurane, followed by stimulation with interleukin-8, phorbol myristate acetate, or chemokine CXC-ligand 1 (CXCL1) to differentiate intracellular pathways. MMP-9 release and activity were quantified by enzyme-linked immunosorbent assay and zymography, respectively. CXC-receptor-2 (CXCR2) expression and phosphorylation of extracellular signal-regulated kinases 1/2 were assessed by flow cytometry. The impact of MMP-9 on the invasion of neutrophils and MC-38 colon cancer cells was assessed using Matrigel-coated filters (n = 6). Results Preconditioning reduced interleukin-8-induced MMP-9-release by 41% (±13, 5%, sevoflurane) and 40% (±13%, desflurane). This was also evident following stimulation of CXCR2 with CXCL1. No impact on phosphorylation of extracellular signal-regulated kinases 1/2 and MMP-9 release was observed with receptor-independent stimulation of protein kinase C with phorbol myristate acetate. Preconditioning reduced transmigration of neutrophils and MC-38 tumor cells to baseline levels. Discussion Volatile anesthetics impair neutrophil MMP-9 release and interfere with pathways downstream of CXCR2, but upstream of protein kinase C. Through down-regulation of MMP-9, volatile anesthetics decrease Matrigel breakdown and reduce subsequent migration of cancer cells in vitro.


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