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cCXCR1 is a receptor for cIL‐8 (9E3/cCAF) and its N‐ and C‐terminal peptides and is also activated by hIL‐8 (CXCL8)
Author(s) -
Li QiJing,
Yao Min,
Dueck Melissa,
Feugate Jo Ellen,
Parpura Vladimir,
MartinsGreen Manuela
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0704398
Subject(s) - biology , chemotaxis , chemokine , chemokine receptor , receptor , microbiology and biotechnology , cxc chemokine receptors , c c chemokine receptor type 6 , signal transduction , extracellular , inflammation , interleukin 8 , immunology , biochemistry
Chemokines are chemotactic cytokines that play important roles in immune responses and wound healing, as well as in pathological conditions such as chronic inflammation and tumorigenesis. The chemokines and their receptors are highly conserved and maintain similar functions in different species. One noteworthy exception is the chemokine interleukin (IL)8/CXC ligand 8 and its specific receptor CXCR1, which are found in humans but are not found in the traditional model organisms, mice and rats. As a consequence, we are using model organisms other than mice to study the functions of IL‐8 and CXCR1, as well as the mechanisms involved in receptor activation by IL‐8. Toward this goal, we have isolated and characterized a new receptor that is highly homologous to human (h)CXCR1, which we named chicken (c)CXCR1. To determine whether this receptor is activated by cIL‐8 and its N‐ and C‐terminal peptides and whether it responds to hIL‐8, we expressed cCXCR1 in NIH3T3 cells, which naturally lack this receptor, and used single‐cell Ca 2 + imaging to detect increases in intracellular Ca 2 + and immunoblot analysis to detect extracellular signal‐regulated kinase 1/2 phosphorylation. We show that cIL‐8, its N and C peptides, and hIL‐8 activate cCXCR1. We further show that cIL‐8 and hIL‐8 stimulate chemotaxis of chicken embryonic fibroblasts, cells that express cCXCR1, and that this effect is specific for each chemokine and this receptor. These results strongly suggest that cCXCR1 is the ortholog for hCXCR1 and that chickens can be used as an effective model system to study the functions of IL‐8, its terminal peptides, and its specific receptor CXCR1.