Eosinophil chemotactic factor-L (ECF-L) enhances osteoclast formation by increasing ICAM-1 expression.
Eosinophil chemotactic factor-L (ECF-L) is a novel stimulator of osteoclast (OCL) formation that acts at the differentiation/fusion stage of OCL formation, and is a cofactor for RANK ligand (RANKL). We examined the effects of ECF-L on the intracellular signaling pathways utilized by RANKL, and on the expression of ICAM-1/LFA-1 to determine its mechanism of action. RAW 264.7 and bone marrow cells were treated with RANKL and/or ECF-L Fc protein to determine their effect on NF-kappaB and AP-1 activity. ECF-L by itself only modestly increased NF-kappaB binding and JNK activity in RAW 264.7 cells, which were further enhanced by RANKL. In contrast, ECF-L Fc increased LFA-1alpha and ICAM-1 mRNA levels 1.8-fold in mouse marrow cultures, and anti-ICAM-1 almost completely inhibited OCL formation induced by 10(-10) M 1,25-(OH)2D3, and ECF-L Fc. Furthermore, ECF-L Fc did not enhance OCL formation by ICAM-1 knockout (KO) cells. Increased expression of ICAM-1 by ECF-L appears to be critical for its effects on OCL formation.
Garcia-Palacios
Veronica
V
Medicine/Hematology-Oncology (111-H), University Drive C, Pittsburgh, PA 15240, USA.
Chung
Ho Yeon
HY
Choi
Sun Jin
SJ
Kurihara
Noriyoshi
N
Lee
Jun Won
JW
Ehrlich
Lori A
LA
Collins
Robert
R
Roodman
G David
GD
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D018925:Chemokines / Q000494:pharmacology*; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects
D018925:Chemokines; D002631:Chemotactic Factors, Eosinophil; C482719:eosinophil chemotactic factor-L, mouse; D018799:Intercellular Adhesion Molecule-1