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

• Published in: Inflammopharmacology Vol. 26; no. 3; pp. 805 - 815
• Main Authors: Slomiany, B. L., Slomiany, A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2018
• Subjects: Allergology; Animals; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Dermatology; Enzyme Activation - drug effects; Enzyme Activation - physiology; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gastroenterology; Humans; Immunology; Lipopolysaccharides - toxicity; Original Article; Pharmacology/Toxicology; Protein Kinase C-delta - metabolism; Rats; Rheumatology; Syk Kinase - metabolism; Toll-Like Receptor 4 - metabolism; Gastric mucosa; Syk activation; Role of PKCδ; H. pylori
• DOI: 10.1007/s10787-017-0430-4
• ISSN: 0925-4692

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. We show that stimulation of gastric mucosal cells with the LPS leads to localization of Syk with the membrane-associated TLR4 complex and its activation through phosphorylation on Tyr. Furthermore, we reveal that the membrane translocation of Syk upon the LPS stimulation occurs with the involvement of protein kinase Cδ (PKCδ)-mediated phosphorylation of Syk on Ser. Thus, our findings demonstrate that H. pylori LPS-induced up-regulation in Syk activity proceeds through the stage of PKCδ-mediated Syk phosphorylation on Ser, required for its recruitment to the membrane-anchored TLR4, followed by the kinase activation through phosphorylation on Tyr. Hence, the phase of PKCδ-mediated Syk phosphorylation on Ser affects the extent of amplification in gastric mucosal inflammatory response to H. pylori.