Downregulation of immunomodulator gene expression in LPS-stimulated human polymorphonuclear leukocytes by the proton pump inhibitor lansoprazole.
Lansoprazole (LPZ) has anti-inflammatory activity and repairs cells damaged by phagocytic cells. In the present study, we evaluated the effects of LPZ on gene expression, especially that of immunomodulator genes, in human polymorphonuclear leukocytes (PMNs) activated by lipopolysaccharide (LPS). Several concentrations of LPZ (final concentrations, 0-10 microg/ml) were added to the PMNs (1 x 10(6) cells/ml), which were stimulated with LPS (100 ng/ml) and incubated at 37 degrees C for 1 or 3 h. When LPS-stimulated PMNs were treated with LPZ at >or=5.0 microg/ml for 1 h, mRNA expression levels of CXCR1/2 and TNFalpha were suppressed in a dose-dependent manner. The gene expression level of CD14 was also downregulated by LPZ at >or=0.1 microg/ml, with expression suppressed to 50% by 10 microg/ml LPZ. However, LPZ at 0.01-5.0 microg/ml had no significant effect on the expression of TLR-4 or CD11b/CD18 mRNA. LPZ at 10 microg/ml downregulated the levels of these mRNAs to 80% and 50%, respectively. On the other hand, when the reaction period was extended to 3 h with the same conditions, all mRNA expression levels were downregulated by >or=0.01 microg/ml LPZ, in a dose-dependent manner. LPZ may suppress the biological functions of PMNs, such as chemotaxis and inflammatory chemokine production.
Ubagai
Tsuneyuki
T
Department of Microbiology and Immunology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. ubat@med.teikyo-u.ac.jp
Koshibu
Yoji
Y
Koshio
Osamu
O
Nakaki
Toshio
T
Ono
Yasuo
Y
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D064747:Lansoprazole; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis / Q000235:genetics; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D039481:CD11b Antigen; D018821:CD18 Antigens; D004791:Enzyme Inhibitors; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D064747:Lansoprazole