Health Effects of Stachybotrys Chartarum – Cytokine Issues



This page lists medical journal articles discussing cytokine issues associated with Stachybotrys exposures.

The Health Effects of Stachybotrys Chartarum page of the Paradigm Change site provides further information on the effects of this toxic mold.


Bhan U, Newstead MJ, Zeng X, Podsaid A, Goswami M, Ballinger MN, Kunkel SL, Standiford TJ. TLR9-dependent IL-23/IL-17 is required for the generation of Stachybotrys chartarum-induced hypersensitivity pneumonitis. Journal of immunology. 2013;190:349–356. PMID: 23180821

In this study, we have developed a murine model of S. chartarum-induced HP that reproduces pathology observed in human HP, and we have hypothesized that TLR9-mediated IL-23 and IL-17 responses are required for the generation of granulomatous inflammation induced by inhaled S. chartarum. Our studies suggest that TLR9 is critical for the development of Th17-mediated granulomatous inflammation in the lung in response to S. chartarum.


Pei R, Gunsch CK. Inflammatory cytokine gene expression in THP-1 cells exposed to Stachybotrys chartarum and Aspergillus versicolor. Environmental toxicology. 2013;28:51–60. PMID: 21384497

Cytokine mRNA expression patterns were investigated in the human monocytic THP-1 cell line exposed to fungal extracts of various fragment sizes obtained from Stachybotrys chartarum RTI 5802 and/or Aspergillus versicolor RTI 3843, two common and well-studied mycotoxin producing fungi. Cytokine mRNA expression was generally upregulated 2-10 times following a 24 h exposure to fungal extracts. Expression of the proinflammatory interleukin-1β, interleukin-8, and tumor necrosis factor-α genes increased while the anti-inflammatory gene interleukin-10 also increased albeit at very low level, suggesting that negative feedback regulation mechanism of production of proinflammatory cytokines initiated upon 24 h of incubation.


Bhan U, Newstead MJ, Zeng X, Ballinger MN, Standiford LR, Standiford TJ. Stachybotrys chartarum-induced hypersensitivity pneumonitis is TLR9 dependent. The American journal of pathology. 2011;179:2779– 2787. PMID: 21982832

The researchers developed a murine model of Stachybotrys chartarum-induced HP that reproduces pathology observed in human HP and hypothesized that toll receptor-like 9 (TLR9)-mediated dendritic cell responses are required for the generation of granulomatous inflammation induced by inhaled SC. Mice sensitized and challenged with 10(6) SC spores develop granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of neutrophils and CD4(+) and CD8(+) T cells. SC sensitization and challenge resulted in robust pulmonary expression of tumor necrosis factor-α, IL-12, and IFN-γ. SC-mediated granulomatous inflammation required IFN-γ and was TLR9 dependent, because TLR9(-/-) mice displayed reduced peribronchial inflammation, decreased accumulation and/or activation of polymorphonuclear (PMN) and CD4(+) and CD8(+) T cells, and reduced lung expression of type 1 cytokines and chemokines. T-cell production of IFN-γ was IL-12 dependent.


Kankkunen P, Rintahaka J, Aalto A, Leino M, Majuri ML, Alenius H, Wolff H, Matikainen S. Trichothecene mycotoxins activate inflammatory response in human macrophages. Journal of immunology. 2009;182:6418–6425. PMID: 19414795

The researchers examined the effect of S. chartarum and trichothecene mycotoxins on the proinflammatory cytokine response in human macrophages. The results indicate that human macrophages sense trichothecene mycotoxins as a danger signal, which activates caspase-1, and further enables the secretion of IL-1beta and IL-18 from the LPS-primed cells.


Shi Y, Porter K, Parameswaran N, Bae HK, Pestka JJ. Role of GRP78/BiP degradation and ER stress in deoxynivalenol-induced interleukin-6 upregulation in the macrophage. Toxicological sciences : an official journal of the Society of Toxicology. 2009;109:247–255. PMID: 19336499

The purpose of this study was to test the hypothesis that the trichothecene mycotoxin deoxynivalenol (DON) triggers an endoplasmic reticulum (ER) stress response in murine macrophages capable of driving IL-6 gene expression. DON markedly decreased protein levels but not the mRNA levels of glucose-regulated protein (GRP) 78 (BiP), a chaperone known to mediate ER stress. Three other trichothecenes (satratoxin G, roridin, T-2 toxin) and the ribosome inhibitory protein ricin were also found to induce GRP78 degradation suggesting that other translation inhibitors might evoke ER stress.


Mbandi E, Pestka JJ. Deoxynivalenol and satratoxin G potentiate proinflammatory cytokine and macrophage inhibitory protein 2 induction by Listeria and Salmonella in the macrophage. Journal of food protection. 2006;69:1334–1339. PMID: 16786854

The purpose of this research was to test the hypothesis that trichothecene mycotoxins amplify inflammatory responses to foodborne bacterial pathogens. We assessed the capacity of deoxynivalenol (DON) and satratoxin G (SG) to potentiate chemokine and proinflammatory cytokine production in RAW 264.7 murine macrophages induced by Listeria monocytogenes and Salmonella Typhimurium. The results indicate that DON encountered in Fusarium-contaminated food and SG from Stachybotrys-contaminated indoor environments could magnify innate inflammatory responses to foodborne bacterial pathogens.


Pestka J, Zhou HR. Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants. Toxicological sciences : an official journal of the Society of Toxicology. 2006;92:445– 455. PMID: 16687389

Activation of the innate immune system might predispose a host to toxicant-induced inflammation. In vitro macrophage models were employed to investigate the effects of preexposure to Toll-like receptor (TLR) agonists on induction of pro-inflammatory cytokine gene expression by the trichothecene mycotoxin deoxynivalenol (DON) and other toxicants. Amplified proinflammatory mRNA expression was demonstrated in LPS-sensitized RAW 264.7 cells exposed to the microbial toxins satratoxin G, Shiga toxin, and zearalenone as well as the anthropogenic toxicants nickel chloride, triphenyltin, 2,4-dinitrochlorobenzene, and 2,3,7,8-tetrachlorodibenzodioxin. The results suggest that prior TLR activation might render macrophages highly sensitive to subsequent induction of proinflammatory gene expression by xenobiotics with diverse mechanisms of action.


Chung YJ, Jarvis B, Pestka J. Modulation of lipopolysaccharideinduced proinflammatory cytokine production by satratoxins and other macrocyclic trichothecenes in the murine macrophage. Journal of toxicology and environmental health. Part A. 2003;66:379–391. PMID: 12554543

RAW 264.7 murine macrophage cells were treated with various concentrations of satratoxin G (SG), isosatratoxin F (iSF), satratoxin H (SH), roridin A (RA), and verrucarin A (VA) for 48 h in the presence or absence of suboptimal concentra-tion of lipopolysaccharide. These results indicate that low concentrations of macrocyclic trichothecenes super-induce expression of TNF-alpha, whereas higher concentrations of these toxins are cytotoxic and concurrently reduce cytokine production.


Lee MG, Li S, Jarvis BB, Pestka JJ. Effects of satratoxins and other macrocyclic trichothecenes on IL-2 production and viability of EL-4 thymoma cells. Journal of toxicology and environmental health. Part A. 1999;57:459–474. PMID: 10494915

To evaluate the capacity of macrocyclic trichothecenes to alter immune functions, the effects of satratoxin G, H, F, roridin A, and verrucarin A on interleukin 2 (IL-2) production and viability were evaluated in a murine T-cell model. When the data were compared to those found in EL-4 cells for the 8-ketotrichothecene vomitoxin (deoxynivalenol), a common food contaminant, the macrocyclic trichothecenes were at least 100 times more potent. The results indicate that, at low concentrations, macrocyclic trichothecenes as a group could superinduce IL-2 production even while partially decreasing cell viability, whereas higher concentrations suppressed cytokine production and were markedly cytotoxic.


Ruotsalainen M, Hirvonen MR, Hyvärinen A, Meklin T, Savolainen K, Nevalainen A. Cytotoxicity, production of reactive oxygen species and cytokines induced by different strains of Stachybotrys sp. from moldy buildings in RAW264.7 macrophages. Environmental toxicology and pharmacology. 1998;6:193–199. PMID: 21781894

The ability of different strains of the fungus Stachybotrys, isolated from mold problem buildings, to induce cytotoxicity and production of important inflammatory mediators, i.e. nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in RAW264.7 macrophages were studied. The results suggest that, in addition to direct cytotoxic effects of most Stachybotrys sp., some strains of Stachybotrys sp. stimulate production of inflammatory mediators, TNF-α and IL-6 which were associated with low cytotoxicity in RAW264.7 macrophages.


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