title: Inflammasome gene expression alterations in Staphylococcus aureus biofilm-associated chronic rhinosinusitis.
abstract: The role of inflammasomes in chronic inflammation has been the subject of intense research in recent years. Chronic rhinosinusitis (CRS), a persistent inflammatory disease, continues to be investigated hoping that a clearer pathophysiologic description will guide discovery of future treatment modalities. This study investigates the role of inflammasome complexes in CRS patients with Staphylococcus aureus biofilm infection, a key culprit associated with disease severity and recalcitrance.
  
  
  
  Sinonasal tissue samples were collected from CRS patients with (P+) and without (P-) polyps and controls. S. aureus biofilm status was obtained using fluorescence in situ hybridization and classified as biofilm positive (B+) or negative (B-). RNA was analysed using a Human Inflammasome PCR array, profiling the expression of 84 genes involved in inflammasome function.
  
  
  
  Sixteen samples were obtained: 5 B+P+, 5 B-P- and 6 controls. Comparing B+P+ vs. controls showed the greatest number of differentially expressed genes. In particular, Absent in Melanoma 2 (AIM2) was consistently and significantly up-regulated in the B+P+ vs. B-P- and controls. In contrast, when comparing the B-P- vs. controls, no genes showed significant changes.
  
  
  
  Our results indicate the involvement of inflammasome complexes and their signalling pathways in CRS patients with polyps and S. aureus biofilms. In particular, AIM2, activated by intracellular double-stranded DNA, is up-regulated in this group, implying that S. aureus may play a role in intracellular triggering of the inflammasome response. Studies with further patient stratification and assessing corresponding protein expression are needed to further characterize the role of inflammasomes in CRS.
authors.forename: C
authors.initials: C
authors.lastname: Jardeleza
authors.forename: D
authors.initials: D
authors.lastname: Miljkovic
authors.forename: L
authors.initials: L
authors.lastname: Baker
authors.forename: S
authors.initials: S
authors.lastname: Boase
authors.forename: N C W
authors.initials: NC
authors.lastname: Tan
authors.forename: S A
authors.initials: SA
authors.lastname: Koblar
authors.forename: P
authors.initials: P
authors.lastname: Zalewski
authors.forename: M
authors.initials: M
authors.lastname: Rischmueller
authors.forename: S
authors.initials: S
authors.lastname: Lester
authors.forename: A
authors.initials: A
authors.lastname: Drilling
authors.forename: D
authors.initials: D
authors.lastname: Jones
authors.forename: L W
authors.initials: LW
authors.lastname: Tan
authors.forename: P J
authors.initials: PJ
authors.lastname: Wormald
authors.forename: S
authors.initials: S
authors.lastname: Vreugde
mesh_terms: D000328:Adult; D000368:Aged; D018441:Biofilms; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012220:Rhinitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012852:Sinusitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D013203:Staphylococcal Infections / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D058847:Inflammasomes; D012333:RNA, Messenger