Tyrosine kinases and inflammatory signalling.
The activity of tyrosine kinases is central to many cellular processes, and accumulating evidence suggests that their role in inflammation is no less profound. Three main tyrosine kinase families, the Src, Tec and Syk kinase families are intimately involved in TLR signalling, the critical first step in cellular recognition of invading pathogens and tissue damage. Their activity results in changes in gene expression in affected cells. Key amongst these genes are the cytokines, which orchestrate both the duration and extent of inflammation. Tyrosine kinases also play important roles in cytokine function, and are implicated in signalling through both pro- and anti-inflammatory cytokines such as TNF, IL-6 and IL-10. Thus, strategies to modulate tyrosine kinase activity have significant therapeutic potential in combating the chronic inflammatory state that is typical of many major health issues that face us today, including Rheumatoid Arthritis, Cardiovascular disease and cancer. Here we review current knowledge of the role of tyrosine kinases in inflammation with particular emphasis on their role in TLR signalling.
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Theresa H
TH
Kennedy Institute of Rheumatology, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, London W6 8LH, UK.
Smolinska
Maria
M
Gillespie
Justin
J
Urbaniak
Anna M
AM
Foxwell
Brian M J
BM
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D053612:Janus Kinases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D051572:Proto-Oncogene Proteins c-hck / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D019061:src-Family Kinases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000936:Antigen-Antibody Complex; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D051193:Toll-Like Receptors; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D053612:Janus Kinases; D051572:Proto-Oncogene Proteins c-hck; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases