title: Protease activity, localization and inhibition in the human hair follicle.
abstract: OBJECTIVE
  In humans, the process of hair shedding, referred to as exogen, is believed to occur independently of the other hair cycle phases. Although the actual mechanisms involved in hair shedding are not fully known, it has been hypothesized that the processes leading to the final step of hair shedding may be driven by proteases and/or protease inhibitor activity. In this study, we investigated the presence of proteases and protease activity in naturally shed human hairs and assessed enzyme inhibition activity of test materials.
  
  
  METHODS
  We measured enzyme activity using a fluorescence-based assay and protein localization by indirect immunohistochemistry (IHC). We also developed an ex vivo skin model for measuring the force required to pull hair fibres from skin.
  
  
  RESULTS
  Our data demonstrate the presence of protease activity in the tissue material surrounding club roots. We also demonstrated the localization of specific serine protease protein expression in human hair follicle by IHC. These data provide evidence demonstrating the presence of proteases around the hair club roots, which may play a role during exogen. We further tested the hypothesis that a novel protease inhibitor system (combination of Trichogen) and climbazole) could inhibit protease activity in hair fibre club root extracts collected from a range of ethnic groups (U.K., Brazil, China, first-generation Mexicans in the U.S.A., Thailand and Turkey) in both males and females. Furthermore, we demonstrated that this combination is capable of increasing the force required to remove hair in an ex vivo skin model system.
  
  
  CONCLUSIONS
  These studies indicate the presence of proteolytic activity in the tissue surrounding the human hair club root and show that it is possible to inhibit this activity with a combination of Trichogen and climbazole. This technology may have potential to reduce excessive hair shedding.
authors.affiliation: Unilever R&D Colworth, Sharnbrook, Bedfordshire, MK44 1LQ, UK.
authors.forename: R K
authors.initials: RK
authors.lastname: Bhogal
authors.affiliation: Unilever R&D Colworth, Sharnbrook, Bedfordshire, MK44 1LQ, UK.
authors.forename: P E
authors.initials: PE
authors.lastname: Mouser
authors.affiliation: Unilever R&D Colworth, Sharnbrook, Bedfordshire, MK44 1LQ, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Higgins
authors.affiliation: Unilever R&D Port Sunlight, Bebington, CH63 3JW, UK.
authors.forename: G A
authors.initials: GA
authors.lastname: Turner
mesh_terms: D000818:Animals; D005260:Female; D018859:Hair Follicle / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008297:Male; D057057:Serine Proteases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013552:Swine
chemical_list: D015842:Serine Proteinase Inhibitors; D057057:Serine Proteases
keywords: exogen; follicle; hair growth; hair loss; hair shedding; hair treatment; proteases