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, cytok ines, and growth factors. In humans, alopecia androgenetica is a common agi ng process thought to be regulated through complex genetic imbalances, whic h also involve several of these crucial identified factors (and probably ot hers 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 gro wth both in vitro and in vivo. Following such treatments, the in vitro grow th 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 durin g the hair cycle, we attempted to identify and localize MMP in the human pi losebaceous unit. Method We used zymography to observe human hair follicles in culture in vit ro. Results We observed that human hair follicles in culture in vitro mainly an d almost exclusively produce MMP-2 and MMP-9 gelatinolytic activities. Furt hermore, after stimulation with EGF, tumor necrosis factor-alpha (TNF-alpha ), or interleukin-1 alpha (IL-1 alpha), MMP-9 production was strongly incre ased. Using immunohistochemistry, we then precisely localized MMIP-9 in the lower part of the inner root sheath (Henle's layer) of control human anage n hair follicles. Conclusions Cytokine- and EGF-induced upregulation of MMP-9 in the lower ep ithelial compartment of the human hair bulb is a major mechanism through wh ich hair follicle involution, observed in alopecia, may occur.