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IL‐13 regulates vascular cell adhesion molecule‐1 expression in human osteoblasts
Author(s) -
Rifas Leonard,
Cheng SuLi
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10531
Subject(s) - microbiology and biotechnology , cell adhesion molecule , cell adhesion , chemistry , cell , biology , biochemistry
Activated T cells (Act T) produce multiple cytokines that affect osteoblast function as well as osteoclastogenesis. One of these cytokines, IL‐13, is a multifunctional cytokine elaborated by Act T that regulates vascular cellular adhesion molecule (VCAM)‐1 expression in endothelial cells. VCAM‐1 has also been implicated in osteoclast formation by myeloma cells. We therefore studied whether IL‐13 regulates VCAM‐1 in human osteoblastic cells since these cells express RANKL, the major osteoclastogenic factor and osteoclast precursors are found adjacent to osteoblasts. Human T cells were activated in the absence or presence of Cyclosporin A (CsA), an inhibitor of the production of most activated T cell cytokines. Conditioned media were assayed for IL‐13 by ELISA. Act T produced IL‐13 and, unlike other T cell cytokines, this was elevated 3‐fold by CsA. Exposure of human osteoblasts (hOB) to doses of recombinant human IL‐13 (rhIL‐13, 0–10 ng/ml) resulted in an increase of VCAM‐1 mRNA (up to 5‐fold) within 4 h with a maximum stimulation at 1 ng/ml. CsA had no effect on basal hOB VCAM‐1 mRNA expression. Examination of VCAM‐1 on the cell surface of hOB, by immunocytochemistry, revealed increasing levels of surface expression of the protein within 16 h after stimulation with doses of rhIL‐13 (0.1–10 ng/ml) which were reflective of the mRNAs. IL‐6 production was also stimulated in a dose dependent manner with a maximum of 2.5‐fold with 1 ng/ml rhIL‐13 within 16 h. Since both VCAM‐1 and IL‐6 showed similar responses to IL‐13, IL‐6 was examined for its ability to induce VCAM‐1. Immunocytochemistry demonstrated no effect of IL‐6 on VCAM‐1 expression. These data demonstrate that during pathological processes associated with T cell activation, such as rheumatoid arthritis or possibly post‐menopausal osteoporosis, T cells may play a pivotal role in osteoclast precursor adhesion to osteoblasts as a first step prior to RANKL signaling. © 2003 Wiley‐Liss, Inc.