An investigation into the role of Pellino2 in lung inflammation

Pellino1, Pellino2 and Pellino3 form a family of E3 ubiquitin ligases that have been implicated in regulation of innate immune signalling pathways including that employed by IL-1. IL-1 signalling is an important component in the development of emphysema and COPD, for which there is no known cure. In an effort to understand the mechanisms leading to the development of emphysema, wild type and Pellino2- deficient mice were subjected to experimental models of lung injury. The studies suggest an important role for Pellino2 in mediating the early inflammatory response in elastase-induced emphysema. Interestingly whilst early inflammation was suppressed in Pellino2-deficient mice, these mice demonstrated more chronic fibrosis in response to repeated elastase challenge than wild type mice. Equivalent studies were also performed in Pellino3-deficient mice. Unlike Pellino2, Pellino3 does not appear to mediate lung inflammation or fibrosis, at least in response to elastase treatment. The studies demonstrate that these differential functions of Pellino2 and Pellino3 in lung inflammation may be associated with involvement of Pellino2 as a mediator in NLRP3 inflammasome-mediated IL-1β production whereas Pellino3 is without effect in this pathway. As Pellino2 was shown to play a role in the immune response following lung injury, the effect of Pellino2 deficiency on the inflammatory response during respiratory infection with Pseudomonas aeruginosa was examined. Pellino2- deficient mice had improved survival and reduced bacterial load when compared with wild type mice in response to respiratory infection. These data are also discussed in the context of impaired activation of the NLRP3-inflammasome in Pellino2-deficient mice. In conclusion, these studies illustrate a role for Pellino2 in regulating the early immune response in the lung to bacterial infection and injury. The studies also suggest a role for Pellino2 in controlling later pathogenesis and lung fibrosis and highlight the non-redundant nature of Pellino proteins in regulation of the innate immune response.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

National University of Ireland Maynooth

Year dc:date.issued

2018

Author dc:creator

• Finnegan, Clare

Language dc:language

en