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Inflammopharmacology

, Volume 27, Issue 2, pp 203–211 | Cite as

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

  • Bronislaw L. SlomianyEmail author
  • Amalia Slomiany
Review
  • 118 Downloads

Abstract

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. The LPS-induced TLR4 activation and the ensuing phosphorylation of its intracellular tyrosine domain by Src-family kinases not only leads to recruitment to the cytoplasmic domain of TLR4 of adaptor molecules directly involved in propagation of the signaling cascades converging on MAPK and IKK, but also provides a propitious docking site for a non-receptor tyrosine kinase, spleen tyrosine kinase (Syk), the activation of which apparently leads to upregulation in the expression of proinflammatory genes. Here, we review the pathways engaged by H. pylori in the recruitment and interaction of Syk with TLR4 in gastric mucosa, and discuss the cascades involved in Syk-mediated amplification in proinflammatory signaling. We focus, moreover, on the potential role of drugs targeting Syk and TLR4 in the treatment of H. pylori-related gastric disease.

Keywords

Gastric mucosa H. pylori TLR4 Syk Proinflammatory signal amplification Therapeutic agents 

Notes

Compliance with ethical standards

Ethical standards

The authors declare that they have no conflict of interest.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Research Center, C855, Rutgers School of Dental MedicineRutgers, The State University of New JerseyNewarkUSA

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