Inhibition of serine-threonine protein phosphatases in monocyte chemoattractant protein-1 expression in Helicobacter pylori-stimulated gastric epithelial cells.
The reversible phosphorylation of proteins controlled by protein kinases and protein phosphatases is a major mechanism that regulates a wide variety of cellular processes, such as inflammation. It has been reported that the activity of at least 30% of all proteins can be regulated by phosphorylation in eukaryotic cells. Among these proteins, mitogen-activated protein kinases (MAPK) and several transcription factors play pivotal roles in inflammation. We previously demonstrated that Helicobacter pylori in a Korean isolate (HP99) induced proinflammatory chemokine expression by activating MAPK and transcription factors, nuclear factor-kappaB (NF-kappaB), and activator protein-1 (AP-1) in gastric epithelial AGS cells. In an attempt to determine the role of phosphorylation-dephosphorylation in HP99-induced inflammation, we analyzed the expression of protein phosphatases, the activation of MAPK and transcription factors, and the production of chemokine MCP-1 in AGS cells stimulated with HP99 (at a bacteria-cell ratio of 300:1) and cultured in the presence or absence of a nonspecific serine-threonine protein phosphatase inhibitor, okadaic acid (OA). Our results showed that HP99 induced the expression of protein phosphatases, PP1 and PP2A in AGS cells as early as 30 min. HP99 induced the activation of MAPK and AP-1, and the production of monocyte chemoattractant protein-1 (MCP-1), which were augmented by pretreatment with 100 nM of OA. Gastric epithelial cells induced the expression of PP1 and PP2A in response to HP99 presumably as a defense mechanism against inflammatory chemokine expression by inhibiting the activation of MAPK and AP-1.
Chung
Hae-Yun
HY
Department of Food and Nutrition, Yonsei University College of Human Ecology, Seoul 120-749, Korea.
Cha
Boram
B
Kim
Hyeyoung
H
D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005753:Gastric Mucosa / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D005756:Gastritis / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000201:enzymology / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*
D018932:Chemokine CCL2; D010749:Phosphoprotein Phosphatases