期刊
CELLULAR IMMUNOLOGY
卷 267, 期 1, 页码 56-66出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2010.11.004
关键词
Cathepsins; Endosomal proteases; Inflammatory response; Macrophage activation; Toll-like receptors; Signal transduction; Pattern recognition receptors
资金
- National Institutes of Health [P50DA05275, R01ES07199]
- A.D. Williams Trust
- VCU Department of Microbiology and Immunology
- Department of Health and Human Services [T32AI07407]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI018697, T32AI007407] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES007199] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [F32DA005275, P50DA005274] Funding Source: NIH RePORTER
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-1 beta 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. (C) 2010 Elsevier Inc. All rights reserved.
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