The Effect of Aggregatibacter actinomycetemcomitans Leukotoxin on Cell-to-Cell Communication in Human Monocytes
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Periodontitis is a complex and multifactorial dental disease and without proper treatment it eventually leads to the loss of teeth. Individuals with a higher number of Aggregatibacter actinomycetemcomitans in their micro-flora have a greater risk of developing periodontitis and the bacterium is associated with local aggressive periodontitis that affects younger populations. Aa produces a toxic virulent factor named Leukotoxin-A that can activate monocytes by a cellular chain reaction resulting in activation and secretion of IL-1β. This cytokine is an important pro-inflammatory key player for maintaining the metabolic balance in tissue homeostasis, which is also of great importance for the pathogenicity of periodontitis. The aim of this study is to investigate if the effect of LtxA on human monocytes involves activation of cell-to-cell (gap-junction) communication trough opening of the Connexin-43 channels (i.e. Connexons) on the target cell membrane. A human monocyte cell line, THP-1, were exposed to LtxA in combination with and without Carbenoxalone, which is an inhibitor of gap junction communication. The activity of GJC was studied by using FACS (fluorescence activated cell scanner) with the Parachute-technique. The results showed that the THP-1 cells do express Cx43 on their membrane both with and without exposure to lipopolysaccharide. LtxA induces a dose and time dependent increased activity of GJC, which was significantly reduced in presence of Cbx. These effects of LtxA and Cbx indicate a specific induction of GJC through Cx43 channels by LtxA. In conclusion, our results show that the activation of human monocytes by LtxA involves stimulation of increased GJC through connexon channels.
Place, publisher, year, edition, pages
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:umu:diva-97868OAI: oai:DiVA.org:umu-97868DiVA: diva2:777378
Johansson, AndersKelk, Peyman