The effect of alpha lipoic acid on the expression of RAGE and sRAGE in THP-1 cells
Cardiff Metropolitan University
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The binding of Advanced Glycation Endproducts (AGEs) to the Receptor for Advanced Glycation Endproducts (RAGE) has been implicated in the pathogenesis of many inflammatory disorders. The RAGE mediated pathway leads to oxidative stress; which is an imbalance of ROS and antioxidant defence. Contrary to this, soluble RAGE has shown to act as a decoy receptor for AGE to RAGE interaction, thus limiting the inflammatory pathway. Furthermore, alpha lipoic acid, which is an endogenous antioxidant, is suspected to cause anti-inflammatory effects via reducing the ROS pathway, thus causing the down regulation of the RAGE mediated pathway. This study aimed to investigate the effect of alpha lipoic acid on the sRAGE and RAGE mediated pathway in THP-1 cells. The first part of the investigation involved treating THP-1 monocytes and macrophages with two alpha lipoic acid concentrations (1000mmol and 100mmol) through the use of a HumanDuo set - ELISA. This technique was employed to detect the concentration of sRAGE produced by the THP-1 cells. Neither: 1000mmol or 100mmol of alpha lipoic acid demonstrated any significant effect on the expression of sRAGE. The second part of the experiment involved flow cytometry analysis on the effect of two alpha lipoic acid concentrations (500mmol and 100mmol) on surface RAGE expression. Two data sets were used with the addition of two pro-inflammatory cytokines (TNFα and INY). The results showed that addition of INY significantly increased surface RAGE expression (P=0.001). However TNFα did not significantly modulate surface RAGE expression nor did the addition of either alpha lipoic acid concentration to either pro-inflammatory cytokine (P>0.05, two paired t-test). In conclusion, the results of the addition of alpha lipoic acid did not significantly affect the sRAGE or RAGE mediated pathway. However, the study suggests further investigation into alpha lipoic acids role in down regulating RAGE mediated pathogenesis would be beneficial. Alpha lipoic acid could play a vital role in treating inflammatory diseases.
BSc (Hons) Biomedical Science
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