Magenschleimproduktion und Magenschleimhautprotektion

Slomiany, Bronislaw L.; Slomiany, Amalia

doi:10.1007/978-3-662-06526-6_9

Cited by 1 publication

(1 citation statement)

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“…The mechanism of p38-mediated Erk inhibition might relate to high level selectivity of distinct MAPK phosphatases for Erk and p38 (77). The ability of p38 inhibitors to stimulate and/or enhance gastric cell MMP-1 release suggests that they may prove ulcerogenic, consistent with a role for p38 in gastric and oral mucosal healing in humans and rats (78,79). However, in contrast to MMP-1, the ability of p38 inhibitors to inhibit MMP-13 secretion suggests that MMP-13 secretion is positively regulated by p38.…”

Section: Discussionmentioning

confidence: 88%

Matrix Metalloproteinase Secretion by Gastric Epithelial Cells Is Regulated by E Prostaglandins and MAPKs

Pillinger

Marjanović

Kim

et al. 2005

Journal of Biological Chemistry

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Because matrix metalloproteinases (MMPs) play roles in inflammatory tissue injury, we asked whether MMP secretion by gastric epithelial cells may contribute to gastric injury in response to signals involved in Helicobacter pylori-induced inflammation and/or cyclooxygenase inhibition. Tumor necrosis factor (TNF)-␣, interleukin (IL)-1␤, and epidermal growth factor (EGF) stimulated gastric cell MMP-1 secretion, indicating that MMP-1 secretion occurs in inflammatory as well as noninflammatory situations. MMP-1 secretion required activation of the MAPK Erk and subsequent protein synthesis but was down-regulated by the alternate MAPK, p38. In contrast, secretion of MMP-13 was stimulated by TNF-␣/IL-1␤ but not EGF and was Erk-independent and mediated by p38. MMP-13 secretion was more rapid (peak, 6 h) than MMP-1 (peak >30 h) and only partly depended on protein synthesis, suggesting initial release of a pre-existing MMP-13 pool. Therefore, MMP-1 and MMP-13 secretion are differentially regulated by MAPKs. MMP-1 secretion was regulated by E prostaglandins (PGEs) in an Erk-dependent manner. PGEs enhanced Erk activation and MMP-1 secretion in response to EGF but inhibited Erk and MMP-1 when TNF-␣ and IL-1␤ were the stimuli, indicating that the effects of PGEs on gastric cell responses are context-dependent. These data show that secretion of MMPs is differentially regulated by MAPKs and suggest mechanisms through which H. pylori infection and/or cyclooxygenase inhibition may induce epithelial cell signaling to contribute to gastric ulcerogenesis.

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Section: Discussionmentioning

confidence: 88%