An Overall Picture of Chemokine Receptors: Basic Research and Drug Development

Chen, Li; Pei, Gang; Zhang, Wenbo

doi:10.2174/1381612043452749

Cited by 21 publications

(10 citation statements)

References 104 publications

(169 reference statements)

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“…In addition, administration of a humanized anti-␣4 monoclonal antibody has demonstrated efficacy in the treatment of multiple sclerosis and Crohn's disease (Ghosh et al, 2003;Miller et al, 2003). Significant efforts have been devoted to the discovery and development of antagonists for specific chemokine receptors (Chen et al, 2004), such as CCR1 for multiple sclerosis, rheumatoid arthritis, and transplantation (Horuk, 2003); CCR3 for eosinophil migration accompanying asthma (Varnes et al, 2004); CXCR2 antagonists for chronic obstructive pulmonary disease, arthritis, and reperfusion injury (Widdowson et al, 2004); and CCR5 (Horuk, 2003) and CXCR4 (De Clercq, 2003).…”

Section: Discussionmentioning

confidence: 99%

A Novel Cannabinoid Peripheral Cannabinoid Receptor-Selective Inverse Agonist Blocks Leukocyte Recruitment in Vivo

Lunn¹,

Fine²,

Rojas-Triana³

et al. 2005

J Pharmacol Exp Ther

121

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The expression of the cannabinoid peripheral cannabinoid receptor (CB 2 ) receptor on peripheral immune cells suggests that compounds specific for CB 2 might be effective anti-inflammatory agents. In this report, we present the initial biological profiling of a novel triaryl bis-sulfone, Sch.336, which is selective for the human cannabinoid CB 2 receptor (hCB 2 ). Sch.336 is an inverse agonist at hCB 2 , as shown by its ability to decrease guanosine 5Ј-3-O-(thio)triphosphate (GTP␥S) binding to membranes containing hCB 2 , by the ability of GTP␥S to left-shift Sch.336 binding to hCB 2 in these membranes, and by the compound's ability to increase forskolin-stimulated cAMP levels in CHO cells expressing hCB 2 . In these systems, Sch.336 displays a greater potency than that reported for the CB 2 In vitro, Sch.336 impairs the migration of CB 2 -expressing recombinant cell lines to the cannabinoid agonist 2-arachidonylglycerol. In vivo, the compound impairs migration of cells to cannabinoid agonist HU210 [(6aR)-trans-3-(1,1-dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo [b,d] pyran-9-methanol]. Oral administration of the Sch.336 significantly inhibited leukocyte trafficking in several rodent in vivo models, induced either by specific chemokines or by antigen challenge. Finally, oral administration of Sch.336 blocked ovalbumin-induced lung eosinophilia in mice, a disease model for allergic asthma. We conclude that selective cannabinoid CB 2 inverse agonists may serve as novel immunomodulatory agents in the treatment of a broad range of acute and chronic inflammatory disorders in which leukocyte recruitment is a hallmark of disease pathology.The identification of a second cannabinoid receptor present primarily in peripheral immune tissues and cells (Munro et al., 1993) suggested an immunomodulatory role for endocannabinoids independent of the effects mediated by their interaction with the "brain" cannabinoid CB 1 receptor. Libraries of selective compounds now exist, based either on the structure of known ligands for the cannabinoid receptors or on results of random compound library screening (Huffman, 2000). With the help of CB 2 -specific compounds and by characterization of a CB 2 Ϫ/Ϫ mouse strain (Buckley et al., 2000), Article, publication date, and citation information can be found at

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Section: Discussionmentioning

confidence: 99%

A Novel Cannabinoid Peripheral Cannabinoid Receptor-Selective Inverse Agonist Blocks Leukocyte Recruitment in Vivo

Lunn¹,

Fine²,

Rojas-Triana³

et al. 2005

J Pharmacol Exp Ther

121

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“…So far, 18 chemokine receptors and more than 50 chemokines have been reported [Chen et al, 2004]. To test the specificity of andrograpanin, its effect was tested by using of several representative chemokine such as CC chemokines RANTES, MIP-1a, MCP-1, and CXC chemokine IL-8 in two other leukocytes, PBLs and THP-1.…”

Section: Andrograpanin Enhanced Sdf-1a-induced Cell Chemotaxis But Hamentioning

confidence: 99%

Andrograpanin, a compound isolated from anti‐inflammatory traditional Chinese medicine Andrographis paniculata, enhances chemokine SDF‐1α‐induced leukocytes chemotaxis

Wang

Dong

et al. 2005

J of Cellular Biochemistry

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Andrographis paniculata is a traditional Chinese medicine (TCM) that has been effectively used for treatment of infection, inflammation, cold, fever, and diarrhea in China. However, mechanism of its therapeutic function is not well known. In the current study, we showed one of its components, andrograpanin, could enhance chemokine stromal cell-derived factor-1alpha (SDF-1alpha) induced chemotaxis in Jurkat and THP-1 cells. Further study demonstrated that this kind of effect was CXC chemokine receptor-4 (CXCR4) specific, since andrograpanin could not enhance other chemokines, such as RANTES, monocyte chemotactic protein-1 (MCP-1), etc. induced cell chemotaxis. Mechanisms of andrograpanin exerting its effect were not directly in the receptor and G protein coupling level because it had no effect on the binding of SDF-1 to CXCR4, SDF-1 induced G protein activation and adenyly cyclase inhibition. However, receptor internalization might be involved, since we found it significantly reduced SDF-1alpha-induced CXCR4 internalization.

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“…(2) The chemokine receptors, expressed in all vertebrate classes, belong structurally to the large superfamily of class A (rhodopsin-like) seven-transmembrane G-protein coupled receptors, which comprises, among others, receptors with important immunological roles, such as leukotriene, C3a, C5a, and formyl peptide receptors. (3) Signal transduction by chemokine receptors leads to activation of trimeric G proteins (4)(5)(6) and phospholipase C, with a consequent increase of intracellular Ca 2+ . (7) These events culminate in leukocyte activation, characterized by chemotaxis, superoxide anion release, phagocytosis, and degranulation.…”

Section: Introductionmentioning

confidence: 99%

Mutation Patterns in the Chemokine CXC Receptor 4 Gene Subfamily

Panaro

Mitolo

Acquafredda

et al. 2008

Immunopharmacology and Immunotoxicology

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Six representative CXCR4 mRNAs of fish, amphibia, birds, and mammals were selected to study the pattern of conservation/mutation of the individual nt of the coding sequences. According to an arbitrary conservation index ranging from 1 to 6, the indexes of conservation were: 5.04 for the first nt of coding triplets; 5.34 for the second nt of triplets, and 3.75 for the third nt of triplets. The average conservation index of the individual triplets was 4.71. The conservation index of the seven hydrophobic transmembrane domains was 5.60, while the cumulative conservation index of the intracytoplasmic and extracellular domains was 4.63. Separate autocorrelation and power spectral analyses of the series of conservation indexes for the first nt, the second nt and the triplets demonstrated a modest "basic" positive correlation for about the first 20 lags and accordingly some power concentration at the lower frequencies (long periods). Within the triplets, the correlation was studied between the conservation indexes of nt 1 and 2, 1 and 3, and 2 and 3. Correlations of 1 with 3 and 2 with 3 were positive, but in the range of the basic local correlation, whereas the correlation between the first and second nt was significantly higher. This correlation, together with the higher conservation of the second nt as compared to the first (two patterns also found in the formyl peptide receptors), are likely to have been established by selection processes directed towards a functional conservation or a "functional repair."

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An Overall Picture of Chemokine Receptors: Basic Research and Drug Development

Cited by 21 publications

References 104 publications

A Novel Cannabinoid Peripheral Cannabinoid Receptor-Selective Inverse Agonist Blocks Leukocyte Recruitment in Vivo

A Novel Cannabinoid Peripheral Cannabinoid Receptor-Selective Inverse Agonist Blocks Leukocyte Recruitment in Vivo

Andrograpanin, a compound isolated from anti‐inflammatory traditional Chinese medicine Andrographis paniculata, enhances chemokine SDF‐1α‐induced leukocytes chemotaxis

Mutation Patterns in the Chemokine CXC Receptor 4 Gene Subfamily

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