Chemokine receptors inflammation with

Fibrosis is a dynamic progression of dysregulated wound healing that results from chronic inflammation. It is a common pathology regardless of the tissue involved, and therefore, the mechanisms that progress to fibrosis can be widely applied. The recruitment, activation, and proliferation of inflammatory cells and their cooperation with resident cells appears to rely on the action of chemokines and the differential expression of the chemokine receptors by these cells. Thus, chemokine receptors make particularly attractive therapeutic targets. 

The gold-standard assay used for all chemokine receptor inhibitors that reach clinical-phase trials is the chemotaxis functional assay. This assay relies on the ability of chemokines to recruit cells expressing their respective receptor to areas of inflammation. In vitro, this assay was first described in detail by Taub et al. (16) for 24/48-well plates currently, this can be achieved by using 96-well plates. Cells are incubated in the upper chamber with an antagonist for a particular receptor (at different concentrations or with buffer) and challenged to migrate to the lower chamber, which has the relevant chemokine. After 2 to 4 hours of incubation at 37°C, the upper chamber inlet is removed and the cells in the lower chamber quantified by fluorescence with, for example, Calcein AM (Invitrogen, Carlsbad, CA). 

Chemokines constitute a large family of about 50 proteins that interact with about 20 different receptors. Cbemokines play a crucial biological role in inflammation, immunity and viral infection. In spite of certain degree of redundancy, the chemokine system presents several levels of specificity in terms of receptor interaction, target cells and biological functions. The relevance of certain chemokines in specific immune responses is also suggested by the expression of selected chemokine-like proteins or chemokine-receptors by viruses as way to escape host response. 

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