title: Serum concentration and circadian profiles of cathepsins B, H and L, and their inhibitors, stefins A and B, in asthma.
abstract: BACKGROUND
  In order to determine the effect of asthma on serum concentrations of cathepsins B, H and L, and stefins A and B, the circadian and concentration profiles were followed in steroid-independent and steroid-dependent asthmatics before and after 1-week treatment with methylprednisolone and cyclosporin A.
  
  
  METHODS
  Serum samples were taken at 4-h intervals throughout a 24-h period. Cathepsin and stefin concentrations were assayed using specific ELISAs. Data were analysed by one-way ANOVA and least squares fit of 24-h cosine.
  
  
  RESULTS
  Temporal analysis of these proteins revealed little or no significant changes with time over a 24-h period. In comparison to normal sera, cathepsin H concentrations were elevated in all asthmatic patients, concentrations of both stefins were decreased in steroid-independent asthmatics, and stefin A concentrations were increased in steroid-dependent asthmatics before therapy. The effect of methylprednisolone treatment was demonstrated on decreased cathepsin B and increased cathepsin L concentrations in post-therapy serum samples. On the other hand, cyclosporin A treatment led to increased concentrations of cathepsins H and L. However, concentrations of stefins A and B were unaffected.
  
  
  CONCLUSIONS
  This study associated alterations in balance of serum cysteine proteinases and their inhibitors in asthmatic patients, which has raised the possibility of their involvement in asthma pathogenesis. Validated rhythms of cathepsins and stefins in asthmatic sera exhibited temporal differences, which are too small to influence the time of sampling for their quantitative measurement over the course of a day.
authors.affiliation: Department of Biochemical Research and Drug Design, Research and Development Division, KRKA, d.d., Cesta na Brdo 49, 1000 Ljubljana, Slovenia. nina.cimerman@krka.si
authors.forename: N
authors.initials: N
authors.lastname: Cimerman
authors.forename: P
authors.initials: P
authors.lastname: Mesko Brguljan
authors.forename: M
authors.initials: M
authors.lastname: Krasovec
authors.forename: S
authors.initials: S
authors.lastname: Suskovic
authors.forename: J
authors.initials: J
authors.lastname: Kos
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology*; D002401:Cathepsin B / Q000097:blood; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000097:blood*; D002940:Circadian Rhythm; D016572:Cyclosporine / Q000627:therapeutic use; D055312:Cystatin A; D055313:Cystatin B; D015891:Cystatins / Q000097:blood; D003546:Cysteine Endopeptidases / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged
chemical_list: C524994:CSTB protein, human; D055312:Cystatin A; D015891:Cystatins; C026407:CSTA protein, human; D016572:Cyclosporine; D055313:Cystatin B; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534126:CTSH protein, human; D056655:Cathepsin H; D008775:Methylprednisolone