Signaling Cascades Underlying the Effects of Chemokines in Arthritis

It is clear that chemokines mediate their effects via seven-transmembrane domain receptors, a subset of G protein-coupled receptors (GPCRs). Interestingly, recent approaches have allowed study of the potential downstream signaling cascades engaged by these chemokine receptors (66). In rats, arthritis development is associated with increases in tyrosine phosphorylation of CCR1 and CCR2. More interestingly, in immunoprecipitation studies, Janus kinase (JAK-1), signal transducer and activator of transcription 1 (STAT-1), and STAT-3 were associated with CCR1, CCR2, and CCR5 expression at different time points during the disease course. Immunohistologic analysis revealed that CCR5, phosphorylated STAT-1, and phosphorylated STAT-3 are present in different cell types in the inflamed synovial tissue of the joints, including lining cells, macrophages, and endothelial cells (66). Collectively, these studies suggest that effects of the chemokines in RA may be related to the ability of chemokine receptors to engage a wide variety of downstream signaling cascades.

Osteoarthritis

Osteoarthritis

Thank you for deciding to learn more about the disorder, Osteoarthritis. Inside these pages, you will learn what it is, who is most at risk for developing it, what causes it, and some treatment plans to help those that do have it feel better. While there is no definitive “cure” for Osteoarthritis, there are ways in which individuals can improve their quality of life and change the discomfort level to one that can be tolerated on a daily basis.

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