Suppression of CD74 expression and Helicobacter pylori adhesion by auraptene targeting serum starvation-activated ERK1/2 in NCI-N87 gastric carcinoma cells.
Helicobacter pylori (H. pylori) is a major human pathogen and plays a central role in chronic gastritis and gastric cancer. Since the adhesion of H. pylori to the human gastric epithelium is the initial and critical step of its infection, anti-H. pylori adhesion agents may be effective for the prevention and therapy of H. pylori-associated diseases. CD74 has recently been identified as a new receptor for H. pylori urease, and we have previously reported that several citrus components strongly suppressed CD74 expression in NCI-N87 gastric carcinoma cells. We found in this present study that auraptene (citrus coumarin) disrupted serum starvation-induced extracellular signaling-regulated kinase (ERK) 1/2 activation and attenuated H. pylori adhesion and IL-8 production in a co-culture system. In addition, the knockdown of CD74 expression led to a significant decrease of H. pylori adhesion, but unexpectedly increased IL-8 production. However, PD98059 (a MEK1/2 inhibitor) dramatically down-regulated this cytokine, suggesting MEK/ERK-dependent IL-8 production. Our results suggest that auraptene suppressed H. pylori adhesion and resulting chemokine production by disrupting ERK1/2 activation.
Sekiguchi
Hirotaka
H
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Irie
Kazuhiro
K
Murakami
Akira
A
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000378:metabolism; D001422:Bacterial Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D016480:Helicobacter pylori / Q000187:drug effects / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D044967:Serum; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
D000944:Antigens, Differentiation, B-Lymphocyte; D003374:Coumarins; D000949:Histocompatibility Antigens Class II; D016209:Interleukin-8; C045084:invariant chain; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C105832:aurapten