Amantadine inhibits RANTES production by influenzavirus-infected human bronchial epithelial cells.
1. Amantadine can prevent and decrease airway inflammation by inhibiting influenza virus (IV) replication; however, the effect of amantadine on RANTES production by human bronchial epithelial cells (BEC) has not been determined. In the present study, we examined the effect of amantadine on RANTES production and also analysed p38 mitogen-activated protein (MAP) kinase and c-Jun-NH2-terminal kinase (JNK) activation to clarify the mechanism in the effect of amantadine on RANTES production, since we have previously shown that p38 MAP kinase and JNK regulate RANTES production by IV-infected BEC. 2. BEC that had been preincubated with amantadine were infected with IV and then p38 MAP kinase and JNK activation in the cells and RANTES concentrations in the culture supernatants were determined. 3. Amantadine-induced inhibition of virus replication resulted in a decrease in p38 MAP kinase and JNK activity and decreased expression of RANTES in IV-infected cells. 4. Amantadine did not inhibit p38 MAP kinase and JNK activation induced by tumour necrosis factor-alpha (TNF-alpha) as a non-viral stimulus. 5. These results indicate that amantadine inhibits IV infection-induced RANTES production by human BEC and that the inhibition by amantadine of RANTES production might result from an indirect inhibitory effect of amantadine on p38 MAP kinase and JNK activation via the inhibition of virus replication, and we emphasize that amantadine may produce a beneficial effect on controlling bronchial asthma exacerbation caused by IV infection.
Asai
Y
Y
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hashimoto
S
S
Kujime
K
K
Gon
Y
Y
Mizumura
K
K
Shimizu
K
K
Horie
T
T
D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy; D001980:Bronchi / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D004285:Dogs; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009975:Orthomyxoviridae / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D000998:Antiviral Agents; D018946:Chemokine CCL5; D014409:Tumor Necrosis Factor-alpha; D000547:Amantadine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases