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Publication : Cytokines regulate cysteine cathepsins during TLR responses.

First Author  Creasy BM Year  2011
Journal  Cell Immunol Volume  267
Issue  1 Pages  56-66
PubMed ID  21145045 Mgi Jnum  J:168791
Mgi Id  MGI:4938237 Doi  10.1016/j.cellimm.2010.11.004
Citation  Creasy BM, et al. (2011) Cytokines regulate cysteine cathepsins during TLR responses. Cell Immunol 267(1):56-66
abstractText  TLR activation is an important component of innate immunity but also contributes to the severity of inflammatory diseases. Cysteine cathepsins (Cat) B, L and S, which are endosomal and lysosomal proteases, participate in numerous physiological systems and are upregulated during various inflammatory disorders and cancers. Macrophages have the highest cathepsin expression and are major contributors to inflammation and tissue damage during chronic inflammatory diseases. We investigated the impact of TLR activation on macrophage Cat B, L and S activities using live-cell enzymatic assays. TLR2, TLR3 and TLR4 ligands increased intracellular activities of these cathepsins in a differential manner. TLR4-induced cytokines increased proteolytic activities without changing mRNA expression of cathepsins or their endogenous inhibitors. Neutralizing antibodies recognizing TNF-alpha, IL-1beta and IFN-beta differentially eliminated cathepsin upregulation. These findings indicate cytokines induced by MyD88-dependent and -independent signaling cascades regulate cathepsin activities during macrophage responses to TLR stimulation.
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