title: Climbazole increases expression of cornified envelope proteins in primary keratinocytes.
abstract: OBJECTIVE
  Dandruff is a troubling consumer problem characterized by flaking and pruritus of the scalp and is considered a multifactorial condition with sebum, individual susceptibility and the fungus Malassezia all thought to play a part. The condition is commonly treated with shampoo products containing antifungal ingredients such as zinc pyrithione and climbazole. It is hypothesized that these ingredients may be delivering additional scalp skin benefits besides their antifungal activity helping to relieve dandruff effectively. The objective of this study was to evaluate the anti-dandruff ingredient climbazole for potential skin benefits using genomics and in vitro assays.
  
  
  METHODS
  Microarray analysis was performed to profile gene expression changes in climbazole-treated primary human keratinocyte cells. Results were independently validated using qPCR and analysis of protein expression using ELISA and immunocytochemistry.
  
  
  RESULTS
  Microarray analysis of climbazole-treated keratinocytes showed statistically significant expression changes in genes associated with the gene ontology groups encompassing epidermal differentiation, keratinization, cholesterol biosynthesis and immune response. Upregulated genes included a number encoding cornified envelope proteins such as group 3 late-cornified envelope proteins, LCE3 and group 2 small-proline-rich proteins, SPRR2. Protein analysis studies of climbazole-treated primary keratinocytes using ELISA and immunocytochemistry were able to demonstrate that the increase in gene transcripts translated into increased protein expression of these cornified envelope markers.
  
  
  CONCLUSIONS
  Climbazole treatment of primary keratinocytes results in an upregulation in expression of a number of genes including those encoding proteins involved in cornified envelope formation with further studies demonstrating this did translate into increased protein expression. A climbazole-driven increase in cornified envelope proteins may improve the scalp skin barrier, which is known to be weaker in dandruff. These studies suggest climbazole, besides its antifungal activity, is delivering positive skin benefits helping to relive dandruff symptoms effectively.
authors.affiliation: Unilever R&D Colworth, Colworth Science Park, Sharnbrook, Bedfordshire, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Pople
authors.forename: A E
authors.initials: AE
authors.lastname: Moore
authors.forename: D C S
authors.initials: DC
authors.lastname: Talbot
authors.forename: K E
authors.initials: KE
authors.lastname: Barrett
authors.forename: D A
authors.initials: DA
authors.lastname: Jones
authors.forename: F L
authors.initials: FL
authors.lastname: Lim
mesh_terms: D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D007093:Imidazoles; D011506:Proteins; C108286:climbazole
keywords: cell culture; climbazole; cornified envelope; dandruff; scalp; skin barrier; skin physiology/structure