title: Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel.
abstract: BACKGROUND
  Excess cathelicidin and kallikrein 5 (KLK5) have been hypothesized to play a role in the pathophysiology of rosacea.
  
  
  OBJECTIVE
  We sought to evaluate the effects of azelaic acid (AzA) on these elements of the innate immune system.
  
  
  METHODS
  Gene expression and protease activity were measured in laboratory models and patients with rosacea during a 16-week multicenter, prospective, open-label study of 15% AzA gel.
  
  
  RESULTS
  AzA directly inhibited KLK5 in cultured keratinocytes and gene expression of KLK5, Toll-like receptor-2, and cathelicidin in mouse skin. Patients with rosacea showed reduction in cathelicidin and KLK5 messenger RNA after treatment with AzA gel. Subjects without rosacea had lower serine protease activity (SPA) than patients with rosacea. Distinct subsets of patients with rosacea who had high and low baseline SPA were identified, and patients with high baseline exhibited a statistically significant reduction of SPA with 15% AzA gel treatment.
  
  
  CONCLUSIONS
  Study size was insufficient to predict clinical efficacy based on the innate immune response to AzA.
  
  
  CONCLUSIONS
  These results show that cathelicidin and KLK5 decrease in association with AZA exposure. Our observations suggest a new mechanism of action for AzA and that SPA may be a useful biomarker for disease activity.
authors.affiliation: Division of Dermatology, Department of Medicine, University of California-San Diego, San Diego, California.
authors.forename: Alvin B
authors.initials: AB
authors.lastname: Coda
authors.forename: Tissa
authors.initials: T
authors.lastname: Hata
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Miller
authors.forename: David
authors.initials: D
authors.lastname: Audish
authors.forename: Paul
authors.initials: P
authors.lastname: Kotol
authors.forename: Aimee
authors.initials: A
authors.lastname: Two
authors.forename: Faiza
authors.initials: F
authors.lastname: Shafiq
authors.forename: Kenshi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Julie C
authors.initials: JC
authors.lastname: Harper
authors.forename: James Q
authors.initials: JQ
authors.lastname: Del Rosso
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D015331:Cohort Studies; D003998:Dicarboxylic Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005782:Gels; D006801:Humans; D007610:Kallikreins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D012393:Rosacea / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D057057:Serine Proteases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D003998:Dicarboxylic Acids; D005782:Gels; D057057:Serine Proteases; D007610:Kallikreins; C010038:azelaic acid; D054804:Cathelicidins
keywords: AzA; CEA; Clinician Erythema Assessment; DMSO; IGA; Investigator Global Assessment; KLK5; LL-37; SPA; antimicrobial peptides; azelaic acid; cathelicidin; dimethyl sulfoxide; kallikrein 5; mRNA; messenger RNA; rosacea; serine protease; serine protease activity