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Eosinophil Chemotactic Factor‐L (ECF‐L) Enhances Osteoclast Formation by Increasing ICAM‐1 Expression
Author(s) -
PALACIOS VERONICA GARCIA,
CHUNG HO YEON,
CHOI SUN JIN,
KURIHARA NORIYOSHI,
LEE JUN WON,
EHRLICH LORI A.,
COLLINS ROBERT,
ROODMAN G. DAVID
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1346.048
Subject(s) - rankl , osteoclast , chemistry , eosinophil , chemotaxis , microbiology and biotechnology , bone marrow , intracellular , rank ligand , medicine , endocrinology , receptor , biochemistry , biology , activator (genetics) , asthma
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‐κB and AP‐1 activity. ECF‐L by itself only modestly increased NF‐κB binding and JNK activity in RAW 264.7 cells, which were further enhanced by RANKL. In contrast, ECF‐L Fc increased LFA‐1α 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) 2 D 3 , 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.