Syk: a new target for attenuation of Helicobacter pylori-induced gastric mucosal inflammatory responses.

The magnitude of gastric mucosal inflammatory response to H. pylori relies primarily on the extent of its key endotoxin, LPS, engagement of Toll-like receptor-4 (TLR4) and the initiation of signal transduction events converging on mitogen-activated protein kinase (MAPK) and IκB complex (IKK) cascades. These cascades, in turn, exert their control over the assembly of transcription factors, NFκB and AP1, implicated in the induction of the expression of iNOS and COX-2 proinflammatory genes.

Helicobacter pylori LPS-induced gastric mucosal spleen tyrosine kinase (Syk) recruitment to TLR4 and activation occurs with the involvement of protein kinase Cδ.

Spleen tyrosine kinase (Syk) has emerged recently as a major effector of proinflammatory genes expression induced by LPS-elicited TLR4 activation, and manifested by the up-amplification in the production of inflammatory mediators, including PGE2 and NO. Here, we investigated the nature of factors involved in the recruitment and interaction of Syk with TLR4 in gastric mucosa in response to H. pylori LPS.

Role of LPS-elicited signaling in triggering gastric mucosal inflammatory responses to H. pylori: modulatory effect of ghrelin.

Infection with Helicobacter pylori is a primary culprit in the etiology of gastric disease, and its cell-wall lipopolysaccharide (LPS) is recognized as a potent endotoxin responsible for triggering a pattern of the mucosal inflammatory responses. The engagement by the LPS of gastric mucosal Toll-like receptor 4 (TLR4) leads to initiation of signal transduction events characterized by the activation of mitogen-activated protein kinase (MAPK) cascade, induction of phosphoinositide-specific phospholipase C (PLC)/protein kinase C (PKC)/phosphatidylinositol 3-kinase (PI3K) pathway, and up-regulation in Src/Akt. These signaling events in turn exert their influence over H.

Helicobacter pylori-induced changes in microtubule dynamics conferred by α-tubulin phosphorylation on Ser/Tyr mediate gastric mucosal secretion of matrix metalloproteinase-9 (MMP-9) and its modulation by ghrelin.

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.

Role of protein kinase D2 phosphorylation on Tyr in modulation by ghrelin of Helicobacter pylori-induced up-regulation in gastric mucosal matrix metalloproteinase-9 (MMP-9) secretion.

Matrix metalloproteinas-9 (MMP-9) is a glycosylated endopeptidase associated with host reaction to microbial endotoxins and also characterizes gastric mucosal inflammatory response to H. pylori infection. Here, we report on the factors involved in gastric mucosal MMP-9 secretion in response to H.