Modulatory effect of silibinin on cytokines production and fungicidal activity of human monocytes challenged with Paracoccidioides brasiliensis in vitro

• Grant number: 08/08374-9
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2008
• End date: November 30, 2010
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Maria Terezinha Serrão Peraçoli
• Grantee: Maria Terezinha Serrão Peraçoli
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Silibinin is the major active component of silymarin (Silybum marianum), a polyphenolic plant flavonoid that has anti-inflammatory, cytoprotective, anti-fibrotic and anticarcinogenic effects. The modulatory effect of silibinin on monocyte function against P.brasiliensis (Pb18) has not yet been demonstrated. The objective of the present study is to evaluate the effect of this flavonoid on tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor beta (TGF-beta1) and prostaglandin E2 (PGE2) production, on NF-kappa B nuclear transcription factor expression and on fungicidal activity of human monocytes challenged in vitro with the virulent strain of P.brasiliensis (Pb18). Peripheral blood monocytes from healthy individuals, blood donors of Botucatu Medical School, UNESP will be pre-incubated in the absence or presence of different concentrations of silibinin (5 and 50 uM) for 60 min at 37oC and 5% CO2. The cells will be challenged with Pb18 in a ratio of 50 monocytes per one fungus for 4h and 18h. The effect of silibinin on infected monocyte will be determined by: a)production of pro- and anti-inflammatory cytokines (TNF-alpha, IL-10 and TGF-beta1) and PGE2 detected in the supernatant of monocyte cultures by enzyme immunoassay (ELISA); b)expression of TNF-alpha, IL-10, TGF-beta1 and NF-kB expression by flow citometry and c)fungicidal activity of monocytes against Pb18 assessed by fungi recovery after plating. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BANNWART, CAMILA FERREIRA; NAKAIRA-TAKAHAGI, ERIKA; GOLIM, MARJORIE ASSIS; LOPES DE MEDEIROS, LEONARDO TEIXEIRA; ROMAO, MARIANA; WEEL, INGRID CRISTINA; SERRAO PERACOLI, MARIA TEREZINHA. Downregulation of nuclear factor-kappa B (NF-kappa B) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis. Life Sciences, v. 86, n. 23-24, p. 880-886, JUN 5 2010. (08/08374-9)