danger signal,

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2009-Trichothecene Mycotoxins Activate Inflammatory Response in Human

Macrophages1

Päivi Kankkunen, Johanna Rintahaka, Annika Aalto, Marina Leino, Marja-Leena

Majuri, Harri Alenius, Henrik Wolff and Sampsa Matikainen2

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-1 & #946; 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-1 & #946; 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-1 & #946; and IL-18 from the LPS-primed cells.

The costs of publication of this article were defrayed in part by the payment of

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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@...

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; CT, cycle threshold value.

http://www.jimmunol.org/cgi/content/abstract/182/10/6418