Abstract
Neutrophils transmigrate from the blood into inflamed tissue via the interaction of chemokines produced in this tissue with chemokine receptors, such as CXCR1 and CXCR2, that are expressed on the membranes of neutrophils. Subsequently, activation of neutrophils will in turn lead to increased tissue damage and thereby enhanced clinical symptoms of inflammatory diseases like chronic obstructive pulmonary disease, inflammatory bowel disease and psoriasis. Besides chemokines, also the collagen-breakdown product N-acetyl-Proline-Glycine-Proline (N-α-PGP) attracts neutrophils. In a recent article (Weathington et al., 2006) it was suggested that N-α-PGP exerts its effect via CXCR1 and CXCR2. In this study, we show that N-α-PGP, in contrast to CXCL8, does not directly activate or interact with CXCR1 or CXCR2. N-α-PGP was not able to displace the radioligand [125I]CXCL8 from CXCR1 and CXCR2 expressing HEK293T cells or neutrophils. In addition, N-α-PGP did not displace the radioligand [3H]-SB265610, a CXCR2 antagonist, from CXCR2 expressing cells. Furthermore, N-α-PGP was not able to activate G protein signalling in cells expressing CXCR1 and CXCR2. N-α-PGP was also not able to recruit β-arrestin2, an intracellular scaffolding protein involved in G protein-independent signalling, in cells expressing CXCR2. These studies indicate that N-α-PGP is not a ligand of CXCR1 or CXCR2. © 2010 Elsevier B.V.
Original language | English |
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Pages (from-to) | 29-33 |
Number of pages | 5 |
Journal | European Journal of Pharmacology |
Volume | 643 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2010 |
Keywords
- CXCR1
- CXCR2
- Inflammation
- N-α-PGP (N-acetyl-Proline-Glycine-Proline)
- Neutrophil
- beta arrestin 2
- chemokine receptor CXCR1
- chemokine receptor CXCR2
- collagen derivative
- guanine nucleotide binding protein
- interleukin 8
- n acetylpropylglycylproline
- unclassified drug
- article
- HEK293 cell line
- controlled study
- human
- human cell
- ligand binding
- neutrophil chemotaxis
- priority journal
- protein protein interaction
- signal transduction