ELR+ CXC chemokines and their receptors (CXC chemokine receptor 1 and CXC chemokine receptor 2) as new therapeutic targets.
ELR+ CXC chemokines, by direct interaction with their cell surface receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2), are believed to be crucially involved in the direct migration and activation of leukocytes. ELR+ CXC chemokines are supposed to play a key role in several inflammatory diseases and this makes ELR+ CXC chemokines and their receptors attractive therapeutic targets. The first aim of this review is to discuss the potential pathological role of ELR+ CXC chemokines in different pathologies, including ulcerative colitis (UC), ischaemia/reperfusion injury (RI), bronchiolitis obliterans syndrome (BOS) and tumor progression. Moreover, the most recently described inhibitors of ELR+ CXC chemokines and their therapeutic indications will be reviewed. Finally, the mode of action and the potential therapeutical use of reparixin, a new potent and selective inhibitor of CXCR1/2 activity, and its chemical derivatives are also discussed.
Bizzarri
Cinzia
C
Dompé Research Centre, Dompé pha.r.ma. s.p.a., Via Campo di Pile, 67100 L'Aquila, Italy.
Beccari
Andrea Rosario
AR
Bertini
Riccardo
R
Cavicchia
Michela Rita
MR
Giorgini
Simona
S
Allegretti
Marcello
M
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000188:drug therapy / Q000378:metabolism; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism
D019743:Chemokines, CXC; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B