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Trichothecene Mycotoxins Activate Inflammatory Response in Human Macrophages¹

Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, Helsinki, Finland

Damp building-related illnesses have caused concern for years in many countries. Although the problem is extensive, the knowledge of the immunological reactions behind damp building-related illnesses is still quite limited. Trichothecene mycotoxins form one major group of toxins, which possibly contribute to the illnesses. Stachybotrys chartarum is a well-known, but also controversial damp building mold and many strains of this mold are capable of producing trichothecenes. In this report, we have examined the effect of S. chartarum and trichothecene mycotoxins on the proinflammatory cytokine response in human macrophages. As a result, satratoxin-positive S. chartarum activated inflammasome-associated caspase-1, which is needed for proteolytic processing of IL-1β and IL-18. Furthermore, purified trichothecene mycotoxins, roridin A, verrucarin A, and T-2 toxin activated caspase-1, and these mycotoxins also strongly enhanced LPS-dependent secretion of IL-1β and IL-18. The satratoxin-positive strain of S. chartarum and the trichothecenes also triggered the activation of caspase-3, which is an effector caspase of apoptosis. Satratoxin-negative S. chartarum was not able to activate either caspase-1 or caspase-3. In conclusion, our results indicate that human macrophages sense trichothecene mycotoxins as a danger signal, which activates caspase-1, and further enables the secretion of IL-1β and IL-18 from the LPS-primed cells.

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¹ This work was supported by grants from the Medical Society of Finland (Finska läkaresällskapet), the Nummela Foundation, Research Council for Biosciences and Environment of the Academy of Finland, and the Sigrid Juselius Foundation.

² Address correspondence and reprint requests to Dr. Sampsa Matikainen, Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, Helsinki, Finland. E-mail address: sampsa.matikainen{at}ttl.fi

³ Abbreviations used in this paper: DBRI, damp building related illness; PRR, pattern recognition receptor; NLR, NOD-like receptor; DAMP, danger-associated molecular pattern; NLRP3, NLR family, pyrin domain, containing 3; NTC, no template control; C_T, cycle threshold value.