Title
Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections
UMMS Affiliation
Program in Molecular Medicine
Publication Date
2007-08-01
Document Type
Article
Disciplines
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Immunology of Infectious Disease | Molecular Biology
Abstract
Streptococcus pneumoniae (S. pneumoniae) causes high early mortality in pneumococcal pneumonia, which is characterized by acute lung injury (ALI). The molecular mechanisms underlying ALI and the high early mortality remain unknown. Despite recent studies that identify deubiquitinating enzyme cylindromatosis (CYLD) as a key regulator for T cell development, tumor cell proliferation, and NF-kappaB transcription factor signaling, its role in regulating bacteria-induced lethality, however, is unknown. Here, we showed that CYLD deficiency protected mice from S. pneumoniae pneumolysin (PLY)-induced ALI and lethality. CYLD was highly induced by PLY, and it inhibited MKK3-p38 kinase-dependent expression of plasminogen activator inhibitor-1 (PAI-1) in lung, thereby potentiating ALI and mortality. Thus, CYLD is detrimental for host survival, thereby indicating a mechanism underlying the high early mortality of pneumococcal pneumonia.
DOI of Published Version
10.1016/j.immuni.2007.07.011
Source
Immunity. 2007 Aug;27(2):349-60. Link to article on publisher's site
Journal/Book/Conference Title
Immunity
Related Resources
PubMed ID
17723219
Repository Citation
Lim JH, Davis RJ, Li J. (2007). Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections. Davis Lab Publications. https://doi.org/10.1016/j.immuni.2007.07.011. Retrieved from https://escholarship.umassmed.edu/davis/60
Comments
Full author list omitted for brevity. For full list of authors see article.