Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells

• Published in: Biochemical pharmacology 2004, Vol.67 (1), p.167-174
• Main Authors: Mak, Nai-Ki, Leung, Chung-Yee, Wei, Xiao-Yi, Shen, Xiao-Ling, Wong, Ricky Ngok-Shun, Leung, Kwok-Nam, Fung, Ming-Chiu
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Bronchi - cytology; Chemokine CCL5 - biosynthesis; Chemokine CCL5 - genetics; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - virology; Gene Expression Regulation - drug effects; Humans; I-kappa B Proteins - biosynthesis; IkB; Indigo Carmine; Indirubin; Indirubin-3′-oxime; Indoles - chemistry; Indoles - pharmacology; Influenza; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Isatin - pharmacology; Medical sciences; Mitogen-Activated Protein Kinases - biosynthesis; Orthomyxoviridae - physiology; p38 MAP kinase; p38 Mitogen-Activated Protein Kinases; Pharmacology. Drug treatments; RANTES; RNA, Messenger - biosynthesis; RNA, Messenger - drug effects
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2003.08.020

The human bronchial epithelial cells are the primary sites of influenza virus infection. In this study, the effect of indirubin on the expression of the chemokine regulated on activation, normal T cell expressed and secreted (RANTES) by the influenza virus-infected H292 human epithelial cell line was examined. The expression of RANTES mRNA was analyzed using reverse transcription polymerase chain reaction and the concentration of RANTES production was determined by the enzyme-linked immunosorbent assay. At the non-cytotoxic concentrations, indirubin was found to reduce both the expression and production of RANTES in influenza A/NWS/33-infected H292 cells. Inhibition was also observed in influenza virus B/Lee-infected cells. Significant reduction of the expression of IL-8 was not observed after the infection. Indirubin-3′-oxime, a recently developed derivative with kinase inhibitory activity, also mediates a potent inhibitory effect on the expression of RANTES. The influenza virus infection-induced phosphorylation of the nuclear transcription NF-kB regulatory molecule IkBα and the p38 MAP kinase were also found to be inhibited by indirubin-3′-oxime. This finding suggests that indirubin is one of the components in the Chinese medicinal herbs Isatis indigotica and Strobilanthes cusia with immunomodulatory activity on the expression of RANTES.