Seasonal Algal Blooms Produce Stress-Inducing Toxins and Impair the Growth of Normal Lung Cells

Cyanobacterial harmful algal blooms (cHABs) occur in freshwater, and marine waters which pose a world-wide public health threat. Anthropogenic factors such as global climate change are increasing the frequency and intensity of cHABs in water supplies. People who live near, or consume water affected by, cHABs have reported very high rates of allergy, asthma and other inflammatory lung maladies. The current study investigates on how cylidrospermopsin (CSM) a small alkyloid toxin produced during cHABs, affects growth and immunotoxic gene responses in human lung cells. Concentration-response assays revealed that CSM reduces the proliferation of cultured non-malignant human lung fibroblasts, MRC-5, in a dose-dependent fashion. The immunotoxicity-focused PCR array of the cDNA libraries generated from MRC-5 cells exposed to CSM demonstrated an increase in genes associated with protein folding and oxidative stress. To confirm the array results, the expression of ten ER stress-associated genes was determined in the same sample used for the array using qRT-PCR. CHOP, DR5, GADD34, ATF3, ATF4, ATF5 were significantly increased confirming the activation of ER stress. Increased expression of NOXA, TRB3 and DR5 further suggested that the antiproliferative mechanism of CSM might be, at least in part, through induction of apoptosis. The role of ER stress in the pathogenesis of asthma has been the focus of many recent reports. The current work has demonstrated that CSM could impede the growth of normal lung cells and led to the intriguing hypothesis that the ability of toxins produced during cHABs to modulate lung health may involve ER stress.