Interleukin-4 induces expression of the integrin alpha v beta 3 via transactivation of the beta 3 gene.
Osteoclastic bone resorption is dependent upon cell-matrix recognition. This process is mediated by the integrin alpha v beta 3 whose expression is enhanced, in avian osteoclast precursors, by bone-seeking steroids. The purpose of this study was to determine if bone-modulating cytokines impact on alpha v beta 3 expression by mouse marrow macrophages (BMMs), known to differentiate into osteoclasts. Of the cytokines tested. Interleukin-4 (IL-4) is most effective in increasing beta 3 mRNA levels by a mechanism involving transactivation of the beta 3 gene. Moreover, IL-4 augmented beta 3 mRNA is mirrored by plasma membrane appearance of alpha v beta 3. As IL-4 induces beta 3 and not alpha v mRNA, the beta 3 chain appears to regulate surface expression of the heterodimer. The functional significance of IL-4-induced alpha v beta 3 is underscored by the fact that, while attachment to fibronectin is unaltered, treatment of BMMs with the cytokine enhances alpha v beta 3-mediated binding to vitronectin 5-fold. Expression of this heterodimer by BMMs driven along a non-osteoclastic lineage suggests alpha v beta 3 may play a role in the inflammatory response of macrophages.
Kitazawa
S
S
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Ross
F P
FP
McHugh
K
K
Teitelbaum
S L
SL
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D016023:Integrins / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D051379:Mice; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016024:Receptors, Cytoadhesin / Q000235:genetics* / Q000378:metabolism; D019030:Receptors, Vitronectin; D015533:Transcriptional Activation; D019096:Vitronectin
D016207:Cytokines; D006023:Glycoproteins; D016023:Integrins; D012333:RNA, Messenger; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D019096:Vitronectin; D015847:Interleukin-4