Inhibition of Toll‐Like receptors alters the ability of tributyltin to increase production of interleukin 1 beta by human immune cells

Abstract

Toll‐like receptors (TLR) are integral for activating the innate immune system responsible for initial detection of infection through recognition of pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). MAP Kinases are downstream signaling components that lead to the production of chemokines, type I interferons, and pro‐inflammatory cytokines, such as interleukin 1β (IL‐1β), in response to TLR activation. IL‐1β is a primary pro‐inflammatory cytokine necessary for an appropriate response to injury or infection. Dysregulation of IL‐1β levels leads to chronic inflammation, which is implicated in the development of diseases such as atherosclerosis, cancer, and autoimmunity. Tributyltin (TBT) is an environmental contaminant due to its use as a biocide in numerous products and in anti‐fouling paints. Previous studies have found that exposure to TBT, which is present in human blood, increases the secretion and intracellular concentrations (production) of the pro‐inflammatory cytokine IL‐1β in peripheral blood mononuclear cells (PMBCs) and this increase requires MAPK activation. The current study examines whether the upstream regulators of MAPK activation in immune cell production of IL‐1β, the TLR, are also required for TBT to induce increases in IL‐1β. TLRs were inhibited with compounds specific for selected TLRs and the ability of TBT (100, 50, and 25 nM) to cause increased production of IL‐1β after 24 h of exposure was examined using ELISA and western blot. Results indicate that when TLR are inhibited there is a decrease in TBT‐induced production IL‐β. This suggests that TBT utilizes the TLR to stimulate IL‐1β production.Support or Funding InformationThe National Science Foundation Tennessee Louis Stokes Alliance for Minority Participation (TLSAMP) Bridge to the Doctorate (BD) program