Niide O, Suzuki Y, Yoshimaru T, Inoue T, Takayama T, Ra C.
Fungal metabolite gliotoxin blocks mast cell activation by a
calcium- and superoxide-dependent mechanism: implications for
immunosuppressive activities.
Clin Immunol. 2006 Jan;118(1):108-16. Epub 2005 Oct 6.
Division of Molecular Cell Immunology and Allergology, Advanced
Medical Research Center, Nihon University Graduate School of Medical
Sciences, 30-1 Oyaguchikami-cho Itabashi-ku, Tokyo 173-8610, Japan.
Fungal secondary metabolites such as gliotoxin, an
epipolythiodioxopiperazine toxin produced by pathogenic fungi like
Candida and Aspergillus, possess immunosuppressive activities and have
been thought to contribute to pathology of fungal infections in animals
and humans. Since recent studies show that mast cell plays a crucial
role in the front of host defense, we examined whether fungal secondary
metabolites affected mast cell activation. We found that gliotoxin had
suppressive effects on FcepsilonRI-dependent or -independent mast cell
activation, including degranulation, leukotriene C4 secretion, and TNF-alpha
and IL-13 production. Gliotoxin also suppressed intracellular Ca2+ rise
through store-operated Ca2+ channels with a minimal effect on depletion
of internal Ca2+ stores. Finally, gliotoxin induced intracellular
production of superoxide possibly through a thiol redox cycling, which
appeared to mediate suppressive effects on mast cell activation. These
findings suggest that suppression of mast cell activation might
contribute to the establishment of infections with gliotoxin-producing
fungi.
PMID: 16213796 |
