title: Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients.
abstract: BACKGROUND
  Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge.
  
  
  OBJECTIVE
  To investigate alterations in bronchoalveolar lavage fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure.
  
  
  METHODS
  Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling.
  
  
  RESULTS
  The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q(2) = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles.
  
  
  CONCLUSIONS
  These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.
authors: Respiratory Medicine Unit, Department of Medicine, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. bettina.levanen@ki.se
authors: Bettina
authors: B
authors: Levänen
authors: Nirav R
authors: NR
authors: Bhakta
authors: Patricia
authors: P
authors: Torregrosa Paredes
authors: Rebecca
authors: R
authors: Barbeau
authors: Stefanie
authors: S
authors: Hiltbrunner
authors: Joshua L
authors: JL
authors: Pollack
authors: C Magnus
authors: CM
authors: Sköld
authors: Magnus
authors: M
authors: Svartengren
authors: Johan
authors: J
authors: Grunewald
authors: Susanne
authors: S
authors: Gabrielsson
authors: Anders
authors: A
authors: Eklund
authors: Britt-Marie
authors: BM
authors: Larsson
authors: Prescott G
authors: PG
authors: Woodruff
authors: David J
authors: DJ
authors: Erle
authors: Åsa M
authors: ÅM
authors: Wheelock
mesh_terms: D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000633:toxicity; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics; D004781:Environmental Exposure; D055354:Exosomes / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D053612:Janus Kinases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D050791:STAT Transcription Factors / Q000235:genetics; D013548:Sweden; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D035683:MicroRNAs; D050791:STAT Transcription Factors; D053612:Janus Kinases; D020928:Mitogen-Activated Protein Kinases