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Beschreibung
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Chemokine (Chemoattractant Cytokines) are small peptides that are potent activators andchemo-attractants for leukocyte subpopulations and other non-hemopoietic cells. Chemokine receptors (CCR) belong to the superfamily of G protein-coupled receptors(GPCR), which regulate the trafficking and activation of leukocytes, and operate asco-receptors in the entry of HIV-1 and directing the proliferation and migration of immatureneurons, glia and their precursors (1). Furthermore, chemokine receptors participate in theetiology and progression of various brain disorders, including AIDS dementia,neuro-inflammatory disease and neuroplasia, making them important potentialtherapeutic targets in these cases. Induction of chemokines and infiltration of chemokinereceptor-bearing cells has also been shown in a variety of animal models of renal diseases,as well as in human diseases and allograft rejection (2). Activation of naïve T cells by specific antigen and cytokines, up-regulate cell adhesionmolecules (CAM) as well as chemokine receptors on their surface, which directs them tomigrate towards the inflamed tissues. Several subtypes of CCR have been characterized(Table1). The CCR4 recrptors are activated by its ligand CCL17/TARC. CCR4 has beenimplicated Not complex function parallel to or down stream of the bur1/2 that facilitatetrimethylation of Histone H3 and regulate the transcription activity (3). CCR4 is alsoinvolved in the chodrogenesis of mesenchymal stem cells, this process is influenced bymany molecules including CXCL1, FIT3L, CCR3 and CCR4. The induction of CCR4 positivecell in duodenuim affects the food allergy, in skin-tropic condition, in allergicbronchopulmonary aspergillosis (ABPA) is a rare variant of severe asthma resulting fromhypersensitivity to Aspergillus fumigatus. The expression of CCR4 is decreases in severalautoimmune diseases such as diabetes type1 and rheumatoid arthritis. The CCR4 receptor protein is approximately 45 kDa (360 amino acids) protein which has 7transmembrane domains, characteristic of G-protein coupled receptors. The CCR4receptors are activated by Thymus and activation-regulated chemokine (TARC) that is expressed constitutively in thymus and transiently in stimulated peripheral bloodmononuclear cells. The protein has putative N-glycosylation sites near the extra cellularN-terminal end of the proteins. The protein has a large 3rd intra cellular loop whichinteracts with G-proteins. The short carboxy terminal is intracellular and has putativepost-translational sites.
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