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Inhibition of lipopolysaccharide-induced I-κB degradation and tumor necrosis factor-α expression by acriflavine, an antimicrobial agent by Sung Hee Choi; Joo Yeun Cho; Young Shin Chung; Eun-Kyung Hong; Young-Bok Han; Sang Geon Kim is a Immunology and Microbiology article available to read on EtoBox.

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Acri ̄avine neutral (ACF) has been used for treatment of microbial infections for humans and ®shes. Eects of ACF on the nuclear factor-kB (NF-kB) activation and tumor necrosis factor-a (TNF-a) production by lipopolysaccharide (LPS), an endotoxin, were examined in rat and RAW264.7 cells. Gel retardation analysis revealed that LPS (1 mg/kg) activated NF-kB in the liver, whereas pretreatment of rats with ACF (10 mg/kg) completely prevented the NF-kB activation. Selectivity of the NF-kB DNA binding was con®rmed by immunodepletion with anti-p65 and anti-p50 antibodies. Translocation of NF-kB to the nucleus is preceded by phosphorylation and proteolytic degradation of inhibitor-kBa (I-kBa) subunit. Whereas the level of I-kBa protein was rapidly decreased after treatment of rats with LPS (1 mg/kg), ACF treatment prior to LPS attenuated the decrease in I-kBa protein level. LPS-induced increase in the production of TNF-a, the principal in ̄ammatory mediator, was prevented by ACF pretreatment by 80%. Stimulation of RAW264.7 cells with 1 mg/ml of LPS caused an increase in DNA binding activity of NF-kB, which was 80% inhibited by 1 mg/ml of ACF. LPS reduced I-kBa level in RAW264.7 cells by 77%

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Author

Sung Hee Choi; Joo Yeun Cho; Young Shin Chung; Eun-Kyung Hong; Young-Bok Han; Sang Geon Kim

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 0192-0561)

Published

2000

Language

EN

Field

Immunology and Microbiology (Life Sciences)