Hello everyone I am writing a lab report about TNF-a and LPS. I tried to find journals about this but I can't find anything online and I am really confused why does LPS lead the cells to make TNFa?
Hey Nina,
LPS is a integral component of the cell membrane of gram-negative bacteria. Its basic structure is always the same, but the components may vary greatly between bacterial species.
LPS (and several other bacterial, viral, fungal or helminth components) are so called Pathogen-associated molecular patterns (PAMPs). Simply, components that do not derive from your body but are endogenous to any microbial intruder (in most cases one that makes you sick). Of course, LPS is also found on bacteria that are harmless to us and pathogenicity is not only based on the presence of PAMPs but also on virluence factors that influence cells.
Many cells (but especially immune cells) have membrane-bound or cytosolic receptor molecules that detect PAMPs (including LPS). After binding of LPS to a specific receptor one or more signaling cascades are activated in the cell that lead to different outcomes depending on the cell type. However, in many cell types of the immune system the detection of LPS leads finally to the activation of NF-kB (a transcription factor among others that are activated) and this leads to the prodcution and secretion of a pletora of cytokines and chemokines of wich one is TNF.
For further reading I can recommend the following papers:
Simpson, B.W., Trent, M.S. Pushing the envelope: LPS modifications and their consequences. Nat Rev Microbiol 17, 403–416 (2019) doi:10.1038/s41579-019-0201-x
Ley K, Pramod AB, Croft M, Ravichandran KS and Ting JP (2016) How Mouse Macrophages Sense What Is Going On. Front. Immunol. 7:204. doi: 10.3389/fimmu.2016.00204
O'Neill, L., Golenbock, D. & Bowie, A. The history of Toll-like receptors — redefining innate immunity. Nat Rev Immunol 13, 453–460 (2013) doi:10.1038/nri3446
I hope that helps you. Perhaps some LPS specialists can add more information.
All the best,
Marc
Dear Nina Smith
Check these:
Article Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Produ...
Article LPS-Induced Formation of Immunoproteasomes: TNF-α and Nitric...
http://www.jbc.org/content/272/28/17795.long
I hope they are helpful. GL
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