Abstract:
:Infection with the opportunistic pathogen Pseudomonas aeruginosa is effectively controlled through tightly coordinated inflammation in healthy individuals. Dysregulated inflammation in cystic fibrosis greatly increases susceptibility to P. aeruginosa and lung damage. Recently, we identified regulator of calcineurin-1, a small, conserved protein that suppresses the NFAT pathway by inhibition of calcineurin and functions as a central negative regulator of multiple inflammatory transcription factors after P. aeruginosa lung infection, implying a role for the canonical NFAT pathway in P. aeruginosa infection. Calcineurin is a calcium-calmodulin-responsive phosphatase that dephosphorylates NFAT and promotes NFAT nuclear translocation and transcriptional activity. The contribution of the NFAT pathway to host defense against P. aeruginosa remains poorly characterized. In this study, we found that NFAT was rapidly and transiently activated after P. aeruginosa infection both in vitro and in vivo. Deficiency of calcineurin Aβ caused impaired activation of NFAT and decreased inflammatory cytokine production in vivo. Finally, we demonstrated that the cross-talk between the NFAT and NFкB pathways coordinately transactivate host response genes during P. aeruginosa infection. Together, these results demonstrate for the first time that NFAT is activated through calcineurin and interacts with NFкB after P. aeruginosa lung infection, and contributes to the host inflammatory response.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Pang Z,Junkins RD,MacNeil AJ,McCormick C,Cheng Z,Chen WM,Lin TJdoi
10.1189/jlb.4A0517-197Rsubject
Has Abstractpub_date
2017-12-01 00:00:00pages
1461-1469issue
6eissn
0741-5400issn
1938-3673pii
jlb.4A0517-197Rjournal_volume
102pub_type
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