216 WHO GUIDELINES FOR INDOOR AIR QUALITY: DAMPNESS AND MOULD

Table A2.1. Summary of in vitro studies on the effects of exposure to microbes or their isolates, including studies relevant to microbial exposures in damp buildings

Cell type Exposure

Studies on the effects of bacteria or fungi

Human alveolar Spores of Streptomyces anulatus epithelial cells

Mouse macrophages, Spores or cells of Mycobacterium avium, Mycobacterium terrae, Aspergillus human macrophages, versicolor, Penicillium spinulosum, Stachybotrys chartarum, Bacillus cereus, human alveolar Pseudomonas fluorescen, Streptomyces californicus epithelial cells

Mouse macrophages S. anulatus grown on different building materials

Mouse macrophages Fungal spores of S. chartarum, A. versicolor, P. spinulosum and spores of S. californicus grown on wetted plasterboard

Mouse macrophages Live and heat-killed fungal spores of Aspergillus fumigatus

Studies on the effects of mycotoxins and other microbial products

Mouse macrophages Mycotoxin-extractions of S. chartarum spp. isolated from mouldy buildings

Human PBMC Pure toxins: citrinin, gliotoxin, patulin

Human, mouse and rat Pure toxin: fumonisin B1 neural cell lines

Human monocytes Pure toxins: citrinin, gliotoxin

Hamster lung fibroplasts, Pure toxin: ochratoxin A monkey kidney cells, primary rat kidney cells

Mouse primary cortical Nigerlysin, haemolysin produced by Aspergillus niger neuronal cultures ANNEX 2. SUMMARY OF IN VITRO AND IN VIVO STUDIES 217

Main findings Reference

Induction of cytotoxicity and inflammatory responses (NO, Jussila et al. (1999) IL-6)

All tested bacteria induced inflammatory responses (IL-6, Huttunen et al. (2001, 2003) TNF-α, NO) in mouse macrophages, but only S. californicus and environmental mycobacteria provoked inflammation (NO, IL-6) in human cells. Inflammatory potential of the tested fungi was weak. Human cells were more resistant to cytotoxicity than mouse cells.

The most intense cytotoxic and inflammatory responses Roponen et al. (2001) (NO, TNF-α, IL-6) were induced by spores grown on plasterboard.

The brand, composition and liner and core materials of Murtoniemi et al. (2001b, 2002, 2003) plasterboard affected the inflammatory responses (NO, IL-1β, IL-6 and TNF-α) and cytotoxicity induced by the spores. Incomplete prevention of microbial growth by biocides increased the toxicity of spores of S. chartarum. mRNA expression of TNF-α, MIP-1α, MIP-1β, and MCP-1 after Pylkkänen et al. (2004) exposure to live, but not to heat-killed spores

Isolates of the satratoxin-producing chemotype were Nielsen et al. (2002) highly cytotoxic. Atranone-producing chemotypes induced inflammatory responses, unlike the pure atranones B and D.

Mycotoxins inhibited IFN-γ-producing T cells. Wichmann, Herbarth, Lehmann (2002)

Increased production of ROS in mouse and rat cells; Stockmann-Juvala et al. (2004) decreased GSH levels; increased lipid peroxidation and necrotic cell death in all cell lines

Inhibition of anti-inflammatory IL-10 and relative Johannessen, Nilsen, Lovik (2005) overproduction of pro-inflammatory IL-6 and TNF-α

Induction of apoptosis and oxidative DNA damage in cell Kamp et al. (2005) lines and primary cells

Rapid loss of cell viability Donohue et al. (2006) 218 WHO GUIDELINES FOR INDOOR AIR QUALITY: DAMPNESS AND MOULD

Cell type Exposure TABLE A2.1. CONT. Human, mouse and Pure toxin: fumonisin B1 rat cell lines of neural and glial origin

Mouse alveolar Spore-extracted toxins of S. chartarum macrophages

Human alveolar Pure toxins: citrinin, gliotoxin and lipopolysaccharides epithelial cells

Studies on interactions between microbes and microbial products

Mouse macrophages Spores of S. californicus with spores or cells of separately grown A. versicolor, P. spinulosum, S. chartarum, B. cereus, M. terrae, and P. fluorescens or various toxins of S. chartarum

Mouse macrophages Combinations of S. californicus, S. chartarum, A. versicolor and P. Spinulosum co-cultivated on wetted plasterboards

Mouse macrophages Spores of co-cultivated S. californicus and S. chartarum and known cytostatic agents produced by streptomycetes

Mouse macrophages Amoebae plus spores of S. californicus or Penicillium spinolosum ANNEX 2. SUMMARY OF IN VITRO AND IN VIVO STUDIES 219

Main findings Reference

Caspase-3 activity increased in all cell lines, except human Stockmann-Juvala et al. (2006) cells of neural origin; glial cells were more sensitive.

Toxins induced cytotoxicity, apoptosis, DNA damage and p53 Wang, Yadav (2006) activation.

Reduced intracellular antioxidant GSH and TGF-β1 levels at Johannessen, Nilsen, Lovik (2007) low mycotoxin concentrations

Synergistic increase in IL-6 production only when Huttunen et al. (2004) macrophages were concomitantly exposed to S. chartarum and S. californicus. Of the toxins of S. chartarum tested, trichodermin and 7-α-hydroxytrichodermol produced a similar synergistic response with S. californicus.

Co-cultivation of S. chartarum and A. versicolor synergistically Murtoniemi et al. (2005) increased the cytotoxicity of the spores.

Microbial interactions during co-cultivation potentiated Penttinen et al. (2005b, 2006, 2007) the ability of the spores to induce apoptosis, cell cycle arrest, DNA damage, p53 accumulation and cytotoxicity in macrophages. The cytostatic agents tested induced similar responses, but not the spores of separately grown microbes.

Amoebae potentiated the cytotoxic and inflammatory (NO, Yli-Pirilä et al. (2007) IL-6, TNF-α) properties of the microbial spores.