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1. Introduction
2. What are chemokines?
3. Chemokines act on 7 TM receptors
4. Chemokines have 2 essential interactions
5. Cellular recruitment is an orchestrated process
6. Receptor-ligand interactions
7. Cell type expression of chemokine receptors
8. Other types of chemokine receptors
9. Promiscuity is not redundancy
10. Not all receptor-ligand interactions are equal
11. Chemokine receptor expression on T cells
12. Temporal control of receptor expression
13. Spatial control of chemokine expression
14. Differential activation of RANTES receptors
15. Structural properties of chemokines
16. Chemokines have a conserved monomeric fold
17. Chemokines have a different quaternary structure
18. Most chemokines are very basic
19. Chemokines have different binding capacities
20. Chemokine biology
21. How do we measure chemotaxis in vitro?
22. Intravital microscopy
23. Peritoneal cell recruitment assay
24. Understanding the role of GAG binding in vivo
25. Chemokines beyond inflammation
26. Chemokine biology - development
27. BLR1 in secondary lymphoid architecture
28. CXCR4-/- mice are embryonic lethal
29. Chemokine biology: infectious diseases
30. Chemokines and HIV
31. The essential HIV/cell interactions
32. HIV to AIDS
33. HIV co-receptors
34. Chemokines can inhibit HIV infection
35. Resistance to HIV infection?
36. Therapeutic applications
37. The anti-inflammatory strategy
38. Chemokines in multiple sclerosis
39. The chemokine system as therapeutic targets
40. CCR4 KO: results were opposite to prediction
41. CCR4 KO: airways hyper-reactivity
42. Successful target validation
43. Summary of receptor knock-outs
44. 2-site model
45. Chemotactic activity on human monocytes
46. Met-RANTES
47. Met-RANTES in murine CIA
48. Met-RANTES and kidney transplants
49. Synergistic effects with cyclosporin
50. Met-RANTES attenuates lung inflammation
51. Attenuation of tumour growth by Met-RANTES
52. Chemokine mapping in inflammatory disease
53. Targeting chemokine receptors against HIV
54. What is the most likely mechanism?
55. AOP-RANTES prevents CCR5 from recycling
56. Species cross-reactivity
57. Inhibition of CCR1 by BX471
58. Receptor coverage
59. Where should the inhibitor bind?
60. Receptor coverage is key to efficacy in vivo
61. Small molecules or biologicals?
62. Inhibitory strategies
63. What are the hurdles?
64. Case studies of marketed drugs
65. Do we understand the reasons for failures?
66. Understanding the biology
67. Target selection for RA: CCR2 or CCR1?
68. Small molecules in development
69. Antibodies in development
70. Nature believes in chemokine system inhibition (1)
71. Nature believes in chemokine system inhibition (2)
72. Identification of evasins by expression cloning
73. Chemokine cross-linking assay
74. Evasin-1, -2 and -4 selectivity
75. The bleomycin lung inflammation model
76. Evasin-3 reduces arthritis symptoms
77. Soluble human chemokine binding proteins
78. Evasin-1 and Evasin-3 are structurally distinct
79. Complex of Evasin-1/MIP-1-alpha
80. Evasins are much smaller than viral BPs
81. Conclusions
82. Acknowledgements

Topics Covered

• Chemokines are immune modulators regulating direction of cell migration
• Chemokine receptors are seven transmembrane (7TM) G protein-coupled receptors
• Chemokines need to bind to endothelial expressed proteoglycans for activity in vivo
• Excessive cell recruitment is a hallmark of inflammation
• 7TM receptors are highly druggable targets for the pharmaceutical industry
• Chemokine receptors are an essential co-receptor for HIV infectivity
• Nature uses chemokine binding proteins to iinhibit the chemokine system

Links

Series:

• Cells of the Innate Immune System
• Cytokines

Categories:

• Biochemistry
• Cell Biology
• Immunology

Therapeutic Areas:

• Immunology & Inflammation

Talk Citation

Proudfoot, A. (2012, January 1). Chemokines and their receptors: their biology and therapeutic relevance [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 23, 2024, from https://doi.org/10.69645/ZUMX9315.
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Publication History

• Published on January 1, 2012

Financial Disclosures

• Dr. Amanda Proudfoot has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.