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Synergistic interaction in simultaneous exposure to Streptomyces californicus and Stachybotrys chartarum

Kati Huttunen, Jukka Pelkonen, Kristian Fog Nielsen +3 more2004Environmental Health PerspectivesJournal Article
10.1289/ehp.6701PubMedFree full text
CardiovascularEndocrine (ADH/ACTH/MSH)GastrointestinalHypothalamic-PituitaryImmune/InnateMusculoskeletalNeurologicalOcularRespiratory/Sinus
ActinomycetesBacterial EndotoxinsIndoor Mold (Stachybotrys, Aspergillus, etc.)MycotoxinsVolatile Organic Compounds (VOCs)Water-Damaged Buildings (WDB)

Abstract

The microbial exposure associated with health complaints in moldy houses consists of a heterogeneous group of components, including both living and dead bacteria, fungi, and their metabolites and active compounds. However, little is known about the interactions between different microbes and their metabolites, although the cytotoxicity and inflammatory potential of certain individual microbes have been reported. In this study, we investigated the inflammatory responses of mouse RAW264.7 macrophages after exposure to six indoor air microbes (Aspergillus versicolor, Penicillium spinulosum, Stachybotrys chartarum, Bacillus cereus, Mycobacterium terrae, and Pseudomonas fluorescens) alone and together with the actinomycete Streptomyces californicus. The production of nitric oxide, levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), and cytotoxicity were measured. The coexposure to Sta. chartarum and Str. californicus caused a synergistic increase in the production of IL-6 but not other cytokines. In further experiments, the metabolites from Sta. chartarum or from closely related fungi (atranones B and E, satratoxin G, trichodermin, 7-alpha-hydroxytrichodermol, staplabin, and SMTP-7) and the known fungal toxins sterigmatocystin, citrinin, and ochratoxin A were each tested with Str. californicus. The testing revealed a synergistic response in TNF-alpha and IL-6 production after coexposure to Str. californicus with both trichodermin and 7-alpha-hydroxytrichodermol. Finally, the synergistic inflammatory response caused by Str. californicus and trichodermin together was studied by analyzing for the presence of nuclear factor-kappa-B (NF-kappa-B) in nuclear extracts of the exposed cells. The exposure to Str. californicus induced the binding of NF-kappa-B proteins to the NF-kappa-B consensus sequence as well as to the natural NF-kappa-B site of the IL-6 promoter. Adding trichodermin to the exposure did not increase the DNA binding.

Key Biomarkers

Alpha Melanocyte Stimulating Hormone (MSH)Immunoglobulin E (IgE)LeptinMatrix Metalloproteinase 9 (MMP9)Vascular Endothelial Growth Factor (VEGF)Visual Contrast Sensitivity (VCS)

Symptom Clusters

Appetite swingsConfusionCoughDifficulty with concentrationExcessive thirstFatigueFrequent urinationHeadacheJoint painLight sensitivityMemory lossMood swingsMuscle achesNight sweatsShortness of breathSinus congestionTingling in extremitiesWord finding difficulty

Cited By (16)

  • Co-occurrence of toxic bacterial and fungal secondary metabolites in moisture-damaged indoor environmentsIndoor Air · 2011
  • The biocontaminants and complexity of damp indoor spaces: more than what meets the eyesToxicology and Industrial Health · 2009
  • Sick building syndrome (SBS) and exposure to water-damaged buildings: Time series study, clinical trial and mechanismsNeurotoxicology and Teratology · 2006
  • A water-damaged home and health of occupants: a case studyJournal of Environmental and Public Health · 2012
  • A time-series study of sick building syndrome: chronic, biotoxin-associated illness from exposure to water-damaged buildingsNeurotoxicology and Teratology · 2005
  • Interactions between and can induce apoptosis and cell cycle arrest in mouse RAW264.7 macrophagesToxicology and Applied Pharmacology · 2005
  • Stachybotrys chartarum, Trichothecene Mycotoxins, and Damp Building–Related Illness: New Insights into a Public Health Enigma

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