TLR-dependent hepcidin expression by THP-1 cells in response to LPS and poly I:C
Al Shuraiqi, Rajaa
Cardiff Metropolitan University
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Hepcidin a hepatic peptide hormone mainly produces by the liver tissue, it is also produce in a small amount by other tissue including lung, heart and macrophages. Hepcidin plays a critical role in iron regulation and contributes to the development of anaemia of inflammation. Level of hepcidin is increase during infection and inflammation. Some studies have shown that this elevation is mediated by microbial components activating Toll-like receptor (TLRs). Expression of TLRs is highly in cells of the innate immune system (monocytes, macrophages). It is believed TLR-mediated increase in hepcidin levels allows the immune system to reduce iron availability to pathogens, as microorganisms and mammalian host depend on iron for growth and replication. Among the microbial components known to induce hepcidin in mouse macrophages is lipopolysaccharide (LPS), but little is know if other microbial components alone or in combination can induce hepcidin production in monocytic cells at different stages of differentiation and whether this expression can be linked to the production of specific cytokines. Thus, in this project the ability of THP-I cells to express hepcidin at mRNA level before and after differentiation and in response to the TLR-specific ligands LPS (TLR4) and Poly I:C (TLR3) was tested. Furthermore this work tried to establish a link between cytokines production, after stimulation via TLR3 and TLR4 and hepcidin expression. Result presented here show that before and after differentiation of THP-1 cells into more mature macrophages-like cells using Phorbol 12-myristate 13-acteate (PMA), there was no hepcidin expression. Moreover, after stimulation with LPS and Poly I:C either individually or in a combination no hepcidin expression was detected. It should be noted that this was not a general defect of THP-1 cells as other microbial components were capable of inducing hepcidin at mRNA level. Quantitation of IL-6, IL-8 and TNF-α by ELISA in the culture supernatants under all conditions tested demonstrated that THP-I cells can produce cytokines when activated via TLR3 and TLR4 but no correlation was found between them and hepcidin expression. Further work will be necessary to clarify why only some microbial components are able to induce hepcidin in THP-1 cells and the signaling mechanism that result in its expression.
BSc (Hons) Biomedical Science
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