Undergraduate Researcher Tennessee State University Hermitage, Tennessee, United States
Sahra Gabure (Tennessee State University)| Wendy Wilburn (Tennessee State University)| Margaret Whalen (Tennessee State University)
Triclosan (TCS) is an antimicrobial agent that is incorporated into medical and personal care products such as topical antiseptics, deodorants, toothpastes, antibacterial soaps, dishwashing liquids, acne treatments, makeup, and lotions. TCS is readily absorbed through the skin. The usage of these products, which rely upon direct contact with skin, is a source of exposure to the compound. Studies have found approximately 1 μM of TCS in human blood plasma upon ingestion of TCS-containing mouthwash. Interleukin-1 beta (IL-1β) is an important pro-inflammatory cytokine produced by immune cells such as monocytes and lymphocytes, and plays a critical role in immune response regulation, tissue repair, and cellular growth. Overproduction of IL-1β can contribute to chronic inflammation and inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. IL-1β has also been shown to stimulate tumor development. A previous study in our lab showed that when peripheral blood mononuclear cells (PBMCs) were exposed to 0.05-5 μM of TCS for a period of 24 hours, secretion of IL-1β increased in an ERK 1/2 dependent manner. Mitogen activated protein kinases (MAPKs), such as ERK 1/2, are known to regulate both the secretion and production of IL-1β. The purpose of the current study is to determine whether TCS is stimulating the immune cell’s ability to produce IL-1β (or solely releasing pre-existing stores of this cytokine) as well as the role of ERK 1/2 pathway in any TCS-induced elevation of IL-1β production. PBMCs were exposed to TCS concentrations ranging from 0.05-5 μM for time periods of 30 minutes, 6 hours, or 24 hours. The cellular production (combination of secreted and intracellular levels of IL-1β) in response to this treatment was investigated by using Enzyme Linked Immunosorbent Assays to measure secretion and Western Blots to measure intracellular levels. The results indicate that production of IL-1β was increased at each length of exposure, with the greatest TCS-induced increases seen at 6 h. To investigate the mechanism of this increased production of IL-1β, PBMCs were exposed to MEK inhibitor PD98059 to block ERK1/2 pathway activity. Prior exposure of PBMCs to the MEK inhibitor diminished TCS-induced increases in IL-1β production. Thus, TCS not only stimulates the secretion of IL-1β from immune cells, but also increases production of this potent inflammatory cytokine, which can contribute to several pathologies. TCS-induced increases in IL-1β were shown to be dependent on the ERK 1/2 MAPK pathway.