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Printable Handouts
Navigable Slide Index
- Introduction
- What are chemokines?
- Chemokines act on 7 TM receptors
- Chemokines have 2 essential interactions
- Cellular recruitment is an orchestrated process
- Receptor-ligand interactions
- Cell type expression of chemokine receptors
- Other types of chemokine receptors
- Promiscuity is not redundancy
- Not all receptor-ligand interactions are equal
- Chemokine receptor expression on T cells
- Temporal control of receptor expression
- Spatial control of chemokine expression
- Differential activation of RANTES receptors
- Structural properties of chemokines
- Chemokines have a conserved monomeric fold
- Chemokines have a different quaternary structure
- Most chemokines are very basic
- Chemokines have different binding capacities
- Chemokine biology
- How do we measure chemotaxis in vitro?
- Intravital microscopy
- Peritoneal cell recruitment assay
- Understanding the role of GAG binding in vivo
- Chemokines beyond inflammation
- Chemokine biology - development
- BLR1 in secondary lymphoid architecture
- CXCR4-/- mice are embryonic lethal
- Chemokine biology: infectious diseases
- Chemokines and HIV
- The essential HIV/cell interactions
- HIV to AIDS
- HIV co-receptors
- Chemokines can inhibit HIV infection
- Resistance to HIV infection?
- Therapeutic applications
- The anti-inflammatory strategy
- Chemokines in multiple sclerosis
- The chemokine system as therapeutic targets
- CCR4 KO: results were opposite to prediction
- CCR4 KO: airways hyper-reactivity
- Successful target validation
- Summary of receptor knock-outs
- 2-site model
- Chemotactic activity on human monocytes
- Met-RANTES
- Met-RANTES in murine CIA
- Met-RANTES and kidney transplants
- Synergistic effects with cyclosporin
- Met-RANTES attenuates lung inflammation
- Attenuation of tumour growth by Met-RANTES
- Chemokine mapping in inflammatory disease
- Targeting chemokine receptors against HIV
- What is the most likely mechanism?
- AOP-RANTES prevents CCR5 from recycling
- Species cross-reactivity
- Inhibition of CCR1 by BX471
- Receptor coverage
- Where should the inhibitor bind?
- Receptor coverage is key to efficacy in vivo
- Small molecules or biologicals?
- Inhibitory strategies
- What are the hurdles?
- Case studies of marketed drugs
- Do we understand the reasons for failures?
- Understanding the biology
- Target selection for RA: CCR2 or CCR1?
- Small molecules in development
- Antibodies in development
- Nature believes in chemokine system inhibition (1)
- Nature believes in chemokine system inhibition (2)
- Identification of evasins by expression cloning
- Chemokine cross-linking assay
- Evasin-1, -2 and -4 selectivity
- The bleomycin lung inflammation model
- Evasin-3 reduces arthritis symptoms
- Soluble human chemokine binding proteins
- Evasin-1 and Evasin-3 are structurally distinct
- Complex of Evasin-1/MIP-1-alpha
- Evasins are much smaller than viral BPs
- Conclusions
- 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
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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 December 14, 2024, from https://doi.org/10.69645/ZUMX9315.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Amanda Proudfoot has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Chemokines and their receptors: their biology and therapeutic relevance
Published on January 1, 2012
49 min
A selection of talks on Cell Biology
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