Downregulation of nuclear factor-kappa B (NF-κB) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis

Silibinin is the major active component of silymarin, a polyphenolic plant flavonoid that has anti-inflammatory effects. The modulatory effect of silibinin on monocyte function against Paracoccidioides brasiliensis (Pb18) has not yet been demonstrated. The present study investigated whether the effe...

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Bibliographic Details
Published in:Life sciences (1973) 2010-06, Vol.86 (23), p.880-886
Main Authors: Bannwart, Camila Ferreira, Nakaira-Takahagi, Erika, Golim, Marjorie Assis, de Medeiros, Leonardo Teixeira Lopes, Romão, Mariana, Weel, Ingrid Cristina, Serrão Peraçoli, Maria Terezinha
Format: Article
Language:English
Subjects:
Adult
Anti-Inflammatory Agents - pharmacology
Cell activation
Cells, Cultured
Dinoprostone - biosynthesis
Dinoprostone - physiology
Down-Regulation - drug effects
Down-Regulation - physiology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Interleukin-10 - biosynthesis
Interleukin-10 - physiology
Middle Aged
Monocytes
Monocytes - drug effects
Monocytes - physiology
NF-kappa B - antagonists & inhibitors
NF-kappa B - physiology
NF-κB
Nitric Oxide - biosynthesis
Nitric Oxide - physiology
Paracoccidioides - immunology
Paracoccidioides brasiliensis
Paracoccidioidomycosis - immunology
Signal Transduction - drug effects
Signal Transduction - physiology
Silibinin
Silymarin - pharmacology
TNF-α
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - physiology
Young Adult
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Summary:Silibinin is the major active component of silymarin, a polyphenolic plant flavonoid that has anti-inflammatory effects. The modulatory effect of silibinin on monocyte function against Paracoccidioides brasiliensis (Pb18) has not yet been demonstrated. The present study investigated whether the effect of silibinin on nuclear factor-kappa B (NF-κB) pathways may affect the production of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), transforming growth factor beta (TGF-β1), prostaglandin E 2 (PGE 2), nitric oxide (NO) and fungicidal activity of human monocytes challenged in vitro with Pb18. Peripheral blood monocytes from healthy individuals were treated with silibinin and challenged with Pb18 for 18 h. TNF-α, IL-10, TGF-β1 and PGE 2 expression were determined by immunoenzymatic assay (ELISA) and NO release was determined by the accumulation of nitrite in culture supernatants. Fungicidal activity of monocytes was analyzed after treatment with interferon-gamma plus silibinin and challenge with Pb18. NF-κB activation in cultured monocytes was evaluated by flow cytometry and ELISA. Silibinin partially inhibited p65NF-κB activation as the number of cells expressing this factor was reduced and the concentration of nuclear p65NF-κB was low, compared to untreated controls. The addition of silibinin also resulted in suppression of TNF-α, IL-10, TGF-β1, PGE 2 and NO production but did not affect the fungicidal activity of monocytes against Pb18. Silibinin exerts anti-inflammatory and anti-fibrotic effects on CD14± human monocytes challenged by Pb18 by partial inhibition of p65NF-κB activation.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2010.04.005