Triclosan Induces Thymic Stromal Lymphopoietin in Skin Promoting Th2 Allergic Responses

Abstract

Triclosan is an antimicrobial chemical incorporated into many personal, medical and household products. Approximately, 75% of the U.S. population has detectable levels of triclosan in their urine, and although it is not typically considered a contact sensitizer, recent studies have begun to link triclosan exposure with augmented allergic disease. We examined the effects of dermal triclosan exposure on the skin and lymph nodes of mice and in a human skin model to identify mechanisms for augmenting allergic responses. Triclosan (0%–3%) was applied topically at 24-h intervals to the ear pinnae of OVA-sensitized BALB/c mice. Skin and draining lymph nodes were evaluated for cellular responses and cytokine expression over time. The effects of triclosan (0%–0.75%) on cytokine expression in a human skin tissue model were also examined. Exposure to triclosan increased the expression of TSLP, IL-1β, and TNF-α in the skin with concomitant decreases in IL-25, IL-33, and IL-1α. Similar changes in TSLP, IL1B, and IL33 expression occurred in human skin. Topical application of triclosan also increased draining lymph node cellularity consisting of activated CD86+GL-7+ B cells, CD80+CD86+ dendritic cells, GATA-3+OX-40+IL-4+IL-13+ Th2 cells and IL-17 A+ CD4 T cells. In vivo antibody blockade of TSLP reduced skin irritation, IL-1β expression, lymph node cellularity, and Th2 responses augmented by triclosan. Repeated dermal exposure to triclosan induces TSLP expression in skin tissue as a potential mechanism for augmenting allergic responses.

Triclosan exposure, transformation, and human health effects

“…Rat in vivo studies noted a fall in IL-25 (pro-inflammatory), IL-33 (both pro and anti-inflammatory), and IL-1α (pro-inflammatory) but an rise in pro-inflammatory cytokine IL-1β and TNF-α expression following 3% TCS dermal exposure (Marshall et al 2015). In primary human epidermis tissue, 0.1% TCS elevated TSLP, IL-1β, and IL-1α gene expression (Marshall et al 2015). Further, antimicrobial also increased the number of immune cells in the skin draining lymph node after dermal application to mice (Anderson et al 2016).…”

Novel cutaneous mediators of chemical allergy

“…Additionally, studies have revealed that, although not sensitizing itself, topical exposure to the antimicrobial chemical triclosan augmented the allergic response to ovalbumin (OVA) through a TSLP-mediated pathway in a mouse model of asthma (Anderson et al 2013;Marshall et al 2015). Further investigation demonstrated that triclosan induced abundant expression of S100A8/A9 in the skin, which acts as an endogenous ligand for TLR4.…”

“…This concept has been demonstrated with animal and human-based studies involving filaggrin, a protein involved in the formation of the epidermis (Palmer et al 2006(Palmer et al , 2007Oyoshi et al 2009). It has been suggested that barrier disruption and dysfunction followed by chemical allergen exposure may allow the perturbing agent to activate the epithelium, leading to the production of allergic cytokines (Islam and Luster 2012;Marshall et al 2015).…”

Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition

“…Additional recent epidemiological studies have revealed increased risks due to TCS exposure of gestational diabetes (Ouyang et al, 2018), abnormalities of sperm morphology (Jurewicz et al, 2018) and lowered cognitive test scores in children (Jackson-Browne et al, 2018). The cellular, molecular and biochemical reasons for these health effects of TCS are not completely understood but include mitochondrial toxicity (Ajao et al, 2015;Shim et al, 2016;Weatherly et al, 2016), reactive oxygen species (ROS) generation (Lv et al, 2016), interference with cellular calcium dynamics (Ahn et al, 2008;Cherednichenko et al, 2012;Weatherly et al, 2018), endocrine disruption (Ruszkiewicz, Li, Rodriguez, & Aschner, 2017) and modulation of cytokine gene expression (Marshall et al, 2015;Yueh et al, 2014).…”