The fungal metabolite, citrinin, inhibits lipopolysaccharide/interferon-γ-induced nitric oxide production in glomerular mesangial cells

Int Immunopharmacol. 2010 Dec;10(12):1608-15. doi: 10.1016/j.intimp.2010.09.017. Epub 2010 Oct 20.


The mycotoxin, citrinin (CTN), is a secondary metabolite of the fermented products of Monascus. The mycotoxin can either suppress or stimulate immune responses. In the present study, the immunomodulatory role of CTN in nitric oxide (NO) production, a proinflammatory mediator in the process of inflammation, was investigated. NO is well known as a mediator of immune responses. Overproduction of NO catalyzed by inducible nitric oxide synthase (iNOS) protects host cells against microbial invasion, while aberrant iNOS induction is associated with the pathophysiology of inflammatory events. Herein, we report that CTN significantly suppressed lipopolysaccharide (LPS)/interferon (IFN)-γ-induced NO production in MES-13 cells, a glomerular mesangial cell line. The percentage of NO reduction caused by CTN was far greater than that of the decline in cell viability. CTN decreased iNOS gene and protein expressions in concentration-dependent manners. CTN caused declines in LPS/IFN-γ-induced signal transducer and activator of transcription-1α (STAT-1α) phosphorylation. Furthermore, LPS/IFN-γ's induction of interferon response factor-1 (IRF-1) mRNA expression was inhibited by CTN. Moreover, CTN attenuated IκB-α phosphorylation and reduced NF-κB's translocation to the nuclear fraction. Taken together, our data indicated that CTN significantly suppressed NO and iNOS expressions in MES-13 cells via inhibition of the JAK/STAT-1α and NF-κB signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / enzymology
  • Cell Nucleus / immunology
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Citrinin / isolation & purification
  • Citrinin / pharmacology*
  • Cytosol / drug effects
  • Cytosol / enzymology
  • Cytosol / immunology
  • Cytosol / metabolism
  • Electrophoretic Mobility Shift Assay
  • Gene Expression / drug effects
  • Immunologic Factors / isolation & purification
  • Immunologic Factors / pharmacology*
  • Interferon-gamma / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Mesangial Cells / drug effects*
  • Mesangial Cells / immunology
  • Mesangial Cells / metabolism
  • Mice
  • Monascus / metabolism*
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Immunologic Factors
  • Lipopolysaccharides
  • Nitric Oxide
  • Citrinin
  • Interferon-gamma
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse