TLR-4 dependent hepcidin expression by THP-1 cells in response to LPS
Cardiff Metropolitan University
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Hepcidin is an antimicrobial peptide produced in response to inflammation by hepatocytes. It plays a major role in iron homeostasis by decreasing the movement of iron from cells into the plasma. As iron is vital for bacterial survival, hepcidin is antimicrobial as it withholds vital iron from the pathogen. This study aims to investigate the production of hepcidin by the stimulation of TLR-4 of THP-1 cells in response to the LPS ligand. The THP-1 cells were differentiated into monocytes by stimulation with PMA and were then stimulated with LPS for 3 hours and 6 hours. A RT-PCR was then carried out on the samples, including a negative and positive control, using primers for the hepcidin gene and the GAPDH gene. The resulting samples of cDNA then underwent agarose gel electrophoresis, and were viewed via U.V transillumination. The study shows that monocytes are able to activate the hepcidin gene via the binding of LPS to TLR-4. This indicates that macrophages free in the blood and tissues are able to produce hepcidin immediately after binding to bacteria. It also suggests that LPS is a direct trigger for hepcidin production. As hepcidin is a potent antimicrobial agent, it could have applications for the treatment of antibiotic resistant bacteria. Other treatments could arise from the control of iron in the body, such as new treatments for the iron deposit disease, haemochromatosis, and the anaemia of chronic disease. There is also scope for new treatments for diseases of inflammatory origin, such as arthritis, liver disease and atherosclerosis, as macrophages also produce inflammatory cytokines in response to LPS. Hepcidin is not only the master iron regulator in the body, but is also heavily involved in the innate immune response, and a lesser role in inflammation.
BSc (Hons) Biomedical Science
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