Universidad Peruana Cayetano Heredia

Diverging mechanisms of activation of chemokine receptors revealed by novel chemokine agonists

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dc.contributor.author Sarmiento, J.
dc.contributor.author Shumate, C.
dc.contributor.author Suetomi, K.
dc.contributor.author Ravindran, A.
dc.contributor.author Villegas, L.
dc.contributor.author Rajarathnam, K.
dc.contributor.author Navarro, J.
dc.date.accessioned 2022-01-18T19:34:39Z
dc.date.available 2022-01-18T19:34:39Z
dc.date.issued 2011
dc.identifier.uri https://hdl.handle.net/20.500.12866/11096
dc.description.abstract CXCL8/interleukin-8 is a pro-inflammatory chemokine that triggers pleiotropic responses, including inflammation, angiogenesis, wound healing and tumorigenesis. We engineered the first selective CXCR1 agonists on the basis of residue substitutions in the conserved ELR triad and CXC motif of CXCL8. Our data reveal that the molecular mechanisms of activation of CXCR1 and CXCR2 are distinct: the N-loop of CXCL8 is the major determinant for CXCR1 activation, whereas the N-terminus of CXCL8 (ELR and CXC) is essential for CXCR2 activation. We also found that activation of CXCR1 cross-desensitized CXCR2 responses in human neutrophils co-expressing both receptors, indicating that these novel CXCR1 agonists represent a new class of anti-inflammatory agents. Further, these selective CXCR1 agonists will aid at elucidating the functional significance of CXCR1 in vivo under pathophysiological conditions. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartofseries PLoS ONE
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject controlled study en_US
dc.subject animal cell en_US
dc.subject metabolism en_US
dc.subject non protein expression en_US
dc.subject unclassified drug en_US
dc.subject human cell en_US
dc.subject cytology en_US
dc.subject Protein Binding en_US
dc.subject interleukin 8 en_US
dc.subject Models, Molecular en_US
dc.subject chemistry en_US
dc.subject drug potentiation en_US
dc.subject neutrophil en_US
dc.subject calcium en_US
dc.subject protein structure en_US
dc.subject rabbit en_US
dc.subject amino acid substitution en_US
dc.subject protein motif en_US
dc.subject Neutrophils en_US
dc.subject antiinflammatory agent en_US
dc.subject Chemokines en_US
dc.subject chemical structure en_US
dc.subject amino terminal sequence en_US
dc.subject Calcium en_US
dc.subject cell strain HL 60 en_US
dc.subject chemokine receptor agonist en_US
dc.subject chemokine receptor CXCR1 en_US
dc.subject chemokine receptor CXCR1 agonist en_US
dc.subject chemokine receptor CXCR2 en_US
dc.subject chemokine receptor CXCR2 agonist en_US
dc.subject Endocytosis en_US
dc.subject HL-60 Cells en_US
dc.subject Mutant Proteins en_US
dc.subject Protein Engineering en_US
dc.subject Receptors, Chemokine en_US
dc.subject Receptors, Interleukin-8A en_US
dc.subject skin inflammation en_US
dc.title Diverging mechanisms of activation of chemokine receptors revealed by novel chemokine agonists en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.pone.0027967
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.00
dc.relation.issn 1932-6203


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