Inhibitory effect of polaprezinc on the inflammatory response to Helicobacter pylori.
Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, against H pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation with H pylori water extract (HPE) in a dose-dependent manner from 10(-7) M to 10(-5) M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibit H pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells.
Handa
Osamu
O
Department of Intrernal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yoshida
Norimasa
N
Tanaka
Yukiko
Y
Ueda
Miho
M
Ishikawa
Takeshi
T
Takagi
Tomohisa
T
Matsumoto
Naoyuki
N
Naito
Yuji
Y
Yoshikawa
Toshikazu
T
D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001252:Astringents / Q000494:pharmacology* / Q000627:therapeutic use; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000209:etiology*; D016209:Interleukin-8 / Q000032:analysis; D009504:Neutrophils / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000209:etiology* / Q000517:prevention & control*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D017967:Zinc Compounds; D019287:Zinc Sulfate / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D001252:Astringents; D016209:Interleukin-8; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D019287:Zinc Sulfate; D002336:Carnosine