Induction of monocyte chemoattractant protein 1 by Helicobacter pylori involves NF-kappaB.
Helicobacter pylori stimulates secretion of monocyte chemoattractant protein 1 (MCP-1) from gastric epithelial cells. Secretion of this chemokine may be instrumental in monocyte infiltration of the gastric epithelium that characterizes H. pylori gastritis. The aim of this study was to identify the mechanism by which H. pylori induces MCP-1 production. Induction of MCP-1 mRNA was assessed by reverse transcription-PCR. We used luciferase reporter assays to monitor activation of the MCP-1 gene promoter and electrophoretic mobility shift assays to explore binding of transcription factors to this promoter. H. pylori infection increased MCP-1 mRNA expression from gastric epithelial cells. Induction of MCP-1 mRNA relies on an intact cag pathogenicity island. We identified two closely spaced NF-kappaB-binding sites within the MCP-1 distal enhancer as required for H. pylori-induced MCP-1 gene transcription. H. pylori infection led to the specific activation of NF-kappaB complexes containing p50 and p65. Kinase-deficient mutants of NF-kappaB-inducing kinase (NIK) and IkappaB kinases (IKK) caused suppression of MCP-1 distal enhancer-dependent reporter activity following H. pylori infection. H. pylori infection induces the activation of NF-kappaB via the NIK-IKK signaling complex, leading to MCP-1 gene transcription in gastric epithelial cells.
Mori
N
N
Department of Preventive Medicine and AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. n-mori@net.nagasaki-u
Ueda
A
A
Geleziunas
R
R
Wada
A
A
Hirayama
T
T
Yoshimura
T
T
Yamamoto
N
N
D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005753:Gastric Mucosa / Q000382:microbiology*; D005786:Gene Expression Regulation; D016480:Helicobacter pylori / Q000145:classification / Q000276:immunology / Q000472:pathogenicity*; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D013045:Species Specificity; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
D018932:Chemokine CCL2; D016328:NF-kappa B; D012333:RNA, Messenger