Identification of clustered cells in human hair follicle responsible for MMP-9 gelatinolytic activity: consequences for the regulation of hair growth.
BACKGROUND: The control of human hair follicle growth and differentiation is dependent upon several well-identified factors, including androgens, cytokines, and growth factors. In humans, alopecia androgenetica is a common aging process thought to be regulated through complex genetic imbalances, which also involve several of these crucial identified factors (and probably others not yet characterized), alone or in combination. Among these factors, epidermal growth factor (EGF), as well as pro-inflammatory cytokines, play a pivotal role, as evidenced by their direct inhibitory effects on hair growth both in vitro and in vivo. Following such treatments, the in vitro growth of hair follicles was rapidly arrested and deleterious modifications of hair morphology were also observed. AIM: Because these cytokines act, at least partly, through the induction of matrix metalloproteinases (MMP), and because tissue remodeling occurs during the hair cycle, we attempted to identify and localize MMP in the human pilosebaceous unit. METHOD: We used zymography to observe human hair follicles in culture in vitro. RESULTS: We observed that human hair follicles in culture in vitro mainly and almost exclusively produce MMP-2 and MMP-9 gelatinolytic activities. Furthermore, after stimulation with EGF, tumor necrosis factor-alpha (TNF-alpha), or interleukin-1alpha (IL-1alpha), MMP-9 production was strongly increased. Using immunohistochemistry, we then precisely localized MMP-9 in the lower part of the inner root sheath (Henle's layer) of control human anagen hair follicles. CONCLUSIONS: Cytokine- and EGF-induced upregulation of MMP-9 in the lower epithelial compartment of the human hair bulb is a major mechanism through which hair follicle involution, observed in alopecia, may occur.