Human Follicular Papilla Cells Carry Out Nonadipose Tissue Production of Leptin

Abstract

Leptin, a satiety-regulating cytokine, is predominantly expressed by adipocytes, although recently the nonadipose tissue production of leptin has been reported. To investigate the possibility of leptin production by human scalp hair follicles, we examined leptin production and its mRNA expression by cultured human follicular papilla cells. We isolated 12 human follicular papilla cell lines from different individuals. They were identified by their morphology, their high alpha-smooth-muscle actin expression, their inability to differentiate into adipocytes, and by the lack of mRNA for adipose-specific fatty acid binding protein. All the human follicular papilla cell lines, but not neonatal human dermal fibroblasts, produced significant amounts of leptin demonstrable by enzyme-linked immunosorbent assay. We demonstrated leptin mRNA expression by human follicular papilla cell lines, but not by neonatal human dermal fibroblasts, by reverse transcription polymerase chain reaction. By immunohistochemistry and in situ hybridization, we detected both leptin protein and mRNA at the lower portion of the hair follicle, i.e., hair matrix, inner root sheath of the hair bulb, and human follicular papilla cells. In contrast, the leptin receptor with intracytoplasmic signal sequence was detected in the follicular papilla cells immunohistochemically, and the long isoform of the leptin receptor mRNA was demonstrated in the human follicular papilla cell lines by reverse transcription polymerase chain reaction. Finally, by using these human follicular papilla cell lines, we showed that cytokines such as interleukin-1 beta, tumor necrosis factor alpha, interferon-gamma, and interleukin-4, and growth factors such as epidermal growth factor, basic fibroblast growth factor, and transforming growth factor beta1, but not vascular endothelial growth factor, hepatocyte growth factor, keratinocyte growth factor, and insulin-like growth factor 1, significantly downregulated the production of leptin. These data demonstrated that human follicular papilla cells produce leptin and express the functional leptin receptor in vivo and in vitro, suggesting its autocrine function. Moreover, the regulation pattern of its production by various factors suggests a pivotal role of leptin in hair biology.