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.

NOACs achieved a dominant market share over warfarin within 3 years from receiving reimbursement in Norway. There were significant differences in patient characteristics between drugs and indications.

Tumour necrosis factor (TNF) is produced by primary human macrophages in response to stimulation by exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) via Toll-like receptor (TLR) signalling. However, uncontrolled TNF production can be deleterious and hence it is tightly controlled at multiple stages. We have previously shown that Bruton's tyrosine kinase (Btk) regulates TLR4-induced TNF production via p38 MAP Kinase by stabilising TNF messenger RNA. Using both gene over-expression and siRNA-mediated knockdown we have examined the role of Btk in TLR7/8 mediated TNF production. Our data shows that Btk acts in the TLR7/8 pathway and mediates Ser-536 phosphorylation of p65 RelA and subsequent nuclear entry in primary human macrophages. These data show an important role for Btk in TLR7/8 mediated TNF production and reveal distinct differences for Btk in TLR4 versus TLR7/8 signalling.

In the hen immune system the egg content plays as significant a role in the development of the chick as colostrum does in newborn mammals. One of the most important proteins in this system seems to be the main yolk immunoglobulin IgY. It has been shown that IgY is accompanied by an immunostimulatory polypeptide complex named yolkin. In this report the biological activities of yolkin separated by means of four different procedures are presented. It was shown that yolkin acts as an inducer rather than a modulator of cytokine and nitric oxide release, and does not participate in the protection of cells against destructive effects of reactive oxygen species. However, using the perchloric acid procedure it is possible to obtain a peptide fraction with higher inducing activity, stronger antioxidant properties and ability to decrease the NO level induced by lipopolysaccharide. The results obtained show that it is feasible to select one of the presented methods of yolkin isolation that yields a product of particular activity. The properties of yolk peptides not only indicate their roles in the development of chicks, but can also be useful for the regulation of some immunological disturbances.