We analyzed changes of growth and apoptotic cell death in human hair follicles. In anagen hair follicles, terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick labeling-positive cells were observed in the keratogenous zone of the upper bulb matrix, the inner root sheath, and the companion layer of the outer root sheath. DNA ladder formation was also detected in anagen hair follicles. In catagen hair follicles, the lower bulb matrix cells around the dermal papilla and the outer layer cells of the outer root sheath became strongly positive, showing that apoptosis in catagen hair is distinct from that in anagen hair. We also confirmed the mRNA expression of four caspases (caspase-1, caspase-3, caspase-4, and caspase-7) in anagen hair follicles by reverse transcriptase-polymerase chain reaction and in situ hybridization. When human anagen hair follicles were cultured in the presence of transforming growth factor-beta or tumor necrosis factor-alpha in the serum-free medium, transforming growth factor-beta but not tumor necrosis factor-alpha induced catagen-like morphologic changes, which were indistinguishable from normal catagen hair follicles. Tumor necrosis factor-alpha, however, strongly inhibited the elongation of the hair shaft in a dose-dependent manner, accompanied by abnormal morphology and increased cell death in the bulb matrix cells. Our results suggest that apoptosis in hair follicles involves two different types. One is related to the terminal differentiation of follicular epithelial cells in anagen hair. The other occurs as a major driving force to eliminate the distinct portion of epithelial components in catagen hair. Furthermore, this study strongly indicates that the transforming growth factor-beta pathway is involved in the induction of catagen phase in human hair cycle.

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These results suggest that IL-1 alpha is an important factor in mediating the relationship between environmental humidity and epidermal pathology.

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It has been previously reported that an adenosine receptor-mediated signal-transduction pathway in the dermal papilla cells (DPCs) of hair contributes to minoxidil-induced hair growth. In this study, we investigated this hypothesis further and have elucidated some underlying mechanisms. We performed DNA microarray analyses of DPCs and found that adenosine stimulation increases fibroblast growth factor-7 (FGF-7) gene expression levels by greater than 2-fold. Elevations of the extracellular FGF-7 protein levels were also observed. These upregulations of FGF-7 both at mRNA and protein levels were inhibited by A2b adenosine receptor-specific antagonist, alloxazine, but not by antagonists for other subtypes. In addition, the intracellular cAMP levels were raised by adenosine in a dose-dependent manner. Moreover, an increase of intracellular cAMP augmented the FGF-7 upregulation. Taken together, these results show that adenosine treatment of DPCs upregulates FGF-7 expression via the A2b adenosine receptor and that cAMP acts as one of the second messengers in this pathway. Furthermore, treatment with FGF-7 at concentrations of 10 ng/ml or greater significantly stimulated hair fiber elongation in human scalp hair follicle organ cultures. These data imply that adenosine might stimulate hair growth through FGF-7 upregulation in DPCs.