CXC chemokines in angiogenesis.
A variety of factors have been identified that regulate angiogenesis, including the CXC chemokine family. The CXC chemokines are a unique family of cytokines for their ability to behave in a disparate manner in the regulation of angiogenesis. CXC chemokines have four highly conserved cysteine amino acid residues, with the first two cysteine amino acid residues separated by one non-conserved amino acid residue (i.e., CXC). A second structural domain within this family determines their angiogenic potential. The NH2 terminus of the majority of the CXC chemokines contains three amino acid residues (Glu-Leu-Arg: the ELR motif), which precedes the first cysteine amino acid residue of the primary structure of these cytokines. Members that contain the ELR motif (ELR+) are potent promoters of angiogenesis. In contrast, members that are inducible by interferons and lack the ELR motif (ELR-) are potent inhibitors of angiogenesis. This difference in angiogenic activity may impact on the pathogenesis of a variety of disorders.
Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, USA.
J A
JA
Belperio
M P
MP
Keane
D A
DA
Arenberg
C L
CL
Addison
J E
JE
Ehlert
M D
MD
Burdick
R M
RM
Strieter
D020816:Amino Acid Motifs; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000503:physiopathology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D002908:Chronic Disease; D005355:Fibrosis; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000503:physiopathology; D019707:Receptors, Chemokine / Q000502:physiology; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016209:Interleukin-8; D009363:Neoplasm Proteins; D019707:Receptors, Chemokine