Environmental toxin 4-nonylphenol and autoimmune diseases: using DNA microarray to examine genetic markers of cytokine expression

INTRODUCTION Adverse progression of autoimmune diseases is linked to the dysregulation of cytokines. In this regard we investigated the role of 4-nonylphenol (4-NP), as a potential contributing factor in the development of immune diseases and compared it to estrogens actions since 4-NP may work via estrogen processes. MATERIAL AND METHODS The study made cytokine level expression changes in U937 cells by microarray technology coupled to RT PCR as a validating technique. RESULTS It was determined that 4-NP significantly up-regulated proinflammatory cytokine expression (toll-like-receptor [TLR]-6, TLR-10, interleukin [IL]-1, IL-5, IL-6, IL-17C, IL-23A, IL-8RB, IL-receptor-associated-kinase [IRAK-2], tumor-necrosis-factor-receptor [TNFR]-5, and TNFR-10). Estrogen caused insignificant increases but the changes parralelled that of 4-NP. Simultaneously, 4-NP down-regulated the expression of anti-inflammatory cytokines (IL-4 and IL-10), while estrogen up-regulated them. CONCLUSIONS 4-Nonylphenol may initiate its toxic effects and pose a risk to autoimmunity-prone individuals by eliciting effects up to 4 times more potent than estrogen. Overall, exposure to 4-NP may contribute to autoimmune susceptibility and/or exacerbate existing autoimmune conditions by dys-regulating normal expression of cytokines.