Cyanobacterial toxins and components induce expression of pro-inflammatory cytokines/chemokines and secretion of soluble cell receptors in a 3D skin cell model

Abstract

Abstract Exposure to cyanobacterial toxins has been linked to several diseases and disorders including skin rashes and damage to the liver and kidneys. Previous research has shown that Microcystin-LR, the most common and toxic microcystin in fresh water, induces the NLRP3 inflammasome in response to administration to mice by oral gavage. In this study, we used a Reconstructed Human Epidermis to investigate immune system responses to cyanobacterial exposure. This 3D tissue model consisting of normal, human-derived epidermal keratinocytes was exposed to Spirulina, anatoxin-contaminated lake water, and phycocyanin. The cell supernatant was probed with a multiplex of 38 cytokines/chemokines and 14 soluble receptors to elucidate the immunological response. Our results revealed that: while most proteins were down-regulated, a number were up-regulated; the expression of many proteins were highly correlated and clustered together; and across the case study datasets, multiple cytokines/chemokines (G-CSF, GRO, IL-6, IL-8, and MCP-1) and soluble cell receptors (sCD30, sEGFR, sTNFRII and sVEGFR1, sVEGFR2 and sVEGFR3) were highly expressed when exposed to the toxins. Our findings correspond with preliminarily histological results showing tissue damage when the skin cells were exposed to the cyanobacterial components. This work shows great promise in the ability to examine the immune response to toxic exposures and aids in the development of techniques useful for studying the impact of harmful algal blooms on public health. Future studies will focus on mapping the immune pathway in response to harmful algal bloom exposure and studying the roles of each of the expressed cytokines and soluble cell receptors in the inflammatory response. This work is supported by the United States Environmental Protection Agency.