Fibroblast growth factor-2 and interleukin-4 synergistically induce eotaxin-1 expression in adipose tissue-derived stromal cells.

Abstract

The relationships between eosinophils and adipose tissues are involved in metabolic homeostasis. Eotaxin is a chemokine with potent effects on eosinophil migration. To clarify the mechanisms of eotaxin expression in adipose tissues, we examined the effects of fibroblast growth factor-2 (FGF-2) and interleukin-4 (IL-4) stimulation on eotaxin expression in adipose tissue-derived stromal cells (ASCs), a type of adipocyte progenitor, in vitro. ASCs expressed eotaxin-1 and did not express eotaxin-2 or -3. Eotaxin-1 expression was increased in a concentration-dependent manner following FGF-2 treatment. Additionally, ASCs expressed FGF receptor-1 (FGFR-1) and did not express FGFR-2, -3, or -4. Eotaxin-1 expression was inhibited in cells treated with the FGFR tyrosine kinase inhibitor and extracellular signal-regulated kinase (ERK) inhibitor U0126, even in the presence of FGF-2. Moreover, eotaxin-1 expression was synergistically enhanced by combined treatment with FGF-2 and IL-4 and inhibited in the presence of U0126. Eotaxin-1 expression induced by FGF-2 and IL-4 was involved in ERK activation via FGFR-1 in ASCs. Upregulation of eotaxin expression in adipose tissues could increase eosinophil migration, thereby inducing IL-4 secretion and activation of alternative macrophages and improving glucose homeostasis. These findings provide insights into the mechanisms through which eotaxin mediates metabolic homeostasis in adipose tissues and eosinophils.