PhD Student Tennessee State University Nashville, Tennessee, United States
Aliyah Alcala (Tennessee State University)
Toll-like receptors (TLRs) activate immune responses through recognition of pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). TLR4 is a cell surface receptor that recognizes PAMPs. MAP kinases (MAPK) are downstream signaling components of the TLR pathway that lead to the production of chemokines, type I interferons, and pro-inflammatory cytokines, such as interleukin (IL) 1β and IL-6, in response to TLR activation. IL-1β and IL-6 are pro-inflammatory cytokines necessary for appropriate response to injury or infection. However, inappropriate elevation of IL-1β or IL-6 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 both IL-1β and IL-6 in peripheral blood mononuclear cells (PMBCs) and these increases require MAPK activation. The current study examines whether the upstream regulator of MAPK activation in immune cell production of IL-1β and IL-6, TLR4, is also required for TBT to induce increases in these cytokines. TLR4 was inhibited with the selective inhibitors TAK-242 or C34. The ability of TBT (100, 50, and 25 nM) to cause increased production of IL-1β or IL-6 in control cells versus inhibitor-treated cells after 24 h of exposure was examined using ELISA and western blot. Results indicate that when TLR4 is inhibited there is a decrease in TBT-induced production of both IL-β and IL-6. Thus, either direct or indirect activation of TLR4 by TBT appears to be part of the mechanism by which it can stimulate IL-1β and IL-6 production in human immune cells.