Downregulation of nuclear factor-kappa B (NF-kappaB) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis.
OBJECTIVE
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-kappaB) pathways may affect the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor beta (TGF-beta1), prostaglandin E(2) (PGE(2)), nitric oxide (NO) and fungicidal activity of human monocytes challenged in vitro with Pb18.


METHODS
Peripheral blood monocytes from healthy individuals were treated with silibinin and challenged with Pb18 for 18h. TNF-alpha, IL-10, TGF-beta1 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-kappaB activation in cultured monocytes was evaluated by flow cytometry and ELISA.


RESULTS
Silibinin partially inhibited p65NF-kappaB activation as the number of cells expressing this factor was reduced and the concentration of nuclear p65NF-kappaB was low, compared to untreated controls. The addition of silibinin also resulted in suppression of TNF-alpha, IL-10, TGF-beta1, PGE(2) and NO production but did not affect the fungicidal activity of monocytes against Pb18.


CONCLUSIONS
Silibinin exerts anti-inflammatory and anti-fibrotic effects on CD14+/- human monocytes challenged by Pb18 by partial inhibition of p65NF-kappaB activation.
Bannwart
Camila Ferreira
CF
Departamento de Microbiologia e Imunologia, Instituto de Biociências, UNESP - Univ Estadual Paulista, Botucatu, São Paulo, Brazil. cfbannwart@unesp.br <cfbannwart@unesp.br>
Nakaira-Takahagi
Erika
E
Golim
Marjorie Assis
MA
de Medeiros
Leonardo Teixeira Lopes
LT
Romão
Mariana
M
Weel
Ingrid Cristina
IC
Peraçoli
Maria Terezinha Serrão
MT
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D000077385:Silybin; D015232:Dinoprostone