Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Nicole Ranson, B Sc (Hons)
,
University of Tasmania, Launceston, TAS, Australia
Brent Mitchell, MD
,
Launceston General Hospital, Launceston, Australia
Scott Fanning, MD
,
launceston General Hospital, launceston, Australia
Dale Kunde
,
Human Life Sciences UTAS, Launceston, TAS, Australia
Rajaraman Eri
,
The University of Tasmania, Launceston, TAS, Australia
Background and Aims: Inappropriate innate immune responses to invading bacteria and/or tissue damage contribute to disease development in IBD. The inflammasome complex plays a key role in regulating the host’s immune response by providing a platform for the activation of caspase-1 and the maturation of IL-1β and IL-18. It is hypothesised that inflammasome activation is a key initiating event in the pathogenesis of IBD and hence this study aims to identify the pathways which lead to specific inflammasome complex activation and development of IBD.
Methods: Paired active and quiescent mucosal biopsies were obtained from UC and Crohn’s disease patients at a private hospital in Tasmania, Australia. Inflammasome expression profiles were established relative to healthy controls using qRT-PCR, targeted RNA-sequencing and inflammasome localisation was determined using immunohistochemistry.
Results: Evidence suggests a hierarchical inflammasome expression profile exists for both UC and CD and differences in the cellular localisation of inflammasome proteins, especially NLRP 3 and 6. Furthermore, RNA sequencing has identified SNPs within targeted inflammasome genes which are specific to this Tasmanian cohort.
Significance: Determining inflammasome activators and downstream pathways will direct possible treatment options and establish the therapeutic benefits of targeting specific inflammasomes in the inflammatory bowel diseases.
