Suppression of proinflammatory cytokine production in macrophages by lansoprazole.
Macrophages (MPs) produce increased levels of proinflammatory cytokines in Crohn's disease; these cytokines are thought to play a central role in the occurrence of the disease. Biologics are currently available for anti-cytokine therapy, but treating intestinal inflammation through direct suppression of proinflammatory cytokine production could be more effective. P-ATPase inhibitors have been reported to be anti-inflammatory, and these inhibitors might suppress the production of MP proinflammatory cytokines. In this study, we examined the effect of two types of ATPase inhibitors on the expression patterns of typical proinflammatory cytokines. Peritoneal MPs from 6- to 8-week-old mice were cultured for 48 h in the presence of lansoprazole (P-ATPase inhibitor), bafilomycin A(1) (V-ATPase inhibitor), or the control solvent dimethylsulfoxide. The MPs were then examined for cytokine expression by quantitative real-time polymerase chain reaction (PCR), and culture supernatants were examined for cytokine production with a multiplex assay in a suspension array system. The possible existence of P-ATPase mRNA in MPs was explored using reverse-transcriptase PCR. P-ATPase mRNA was not detected in MP cells. However, all examined proinflammatory cytokines decreased significantly in their mRNA and protein expression in the lansoprazole-treated group. Conversely, bafilomycin A(1) increased the levels of these cytokines. Lansoprazole might be useful for the treatment of inflammatory bowel diseases (IBDs), including Crohn's disease, as it suppresses the production of relevant MP proinflammatory cytokines. However, because P-ATPase was not detected in MPs, the mechanism is unclear and remains to be studied further in an IBD animal model.
Hinoki
Akinari
A
Department of Pediatric Surgery, Saitama Medical School, 38 Morohongo Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan. ahinoki@saitama-med.ac.jp
Yoshimura
Kazunori
K
Fujita
Keiko
K
Akita
Masumi
M
Ikeda
Rie
R
Nagashima
Masabumi
M
Nomura
Masahiko
M
Satomi
Akira
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D064747:Lansoprazole; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D016207:Cytokines; D012333:RNA, Messenger; D064747:Lansoprazole; D000251:Adenosine Triphosphatases