Abstract
Regulation of matrix metalloproteinase-9 (MMP-9) secretion in response to proinflammatory challenge remains under a strict control of factors that affect the stability dynamics of the major cytoskeleton polymeric structures, microtubules (MTs). In this study, we report that H. pylori LPS-elicited induction gastric mucosal MMP-9 secretion is accompanied by the enhancement in MT stabilization as evidenced by the increase in α-tubulin acetylation and detyrosination while the modulatory influence of hormone, ghrelin, is associated with MT destabilization and reflected in a decrease in α-tubulin acetylation and detyrosination. Further, we reveal that the LPS-induced enhancement in MT stabilization and up-regulation in MMP-9 secretion as well as the modulatory influence of ghrelin occur with the involvement of PKCδ and SFK. The LPS effect is reflected in a marked increase in PKCδ-mediated α-tubulin phosphorylation on Ser, while the modulatory effect of ghrelin on MT dynamics and MMP-9 secretion is manifested by the SFK-dependent phosphorylation of α-tubulin on Tyr. Moreover, the changes in α-tubulin phosphorylation and MT stabilization dynamics occur in concert with the Golgi recruitment and activation of PKD2 and Arf-GEF. The findings demonstrate that the enhancement in gastric mucosal MMP-9 secretion in response to H. pylori and its modulation by ghrelin are the result of changes in MT dynamics conferred by PKCδ/SFK- mediated α-tubulin Ser/Tyr phosphorylation.
Original language | English (US) |
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Pages (from-to) | 197-205 |
Number of pages | 9 |
Journal | Inflammopharmacology |
Volume | 24 |
Issue number | 5 |
DOIs | |
State | Published - Oct 1 2016 |
All Science Journal Classification (ASJC) codes
- Immunology
- Pharmacology
- Pharmacology (medical)
Keywords
- Gastric mucosa
- Ghrelin
- H. pylori LPS
- MMP-9
- MT stabilization
- α-tubulin Tyr/Ser phosphorylation