Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections
Program in Molecular Medicine
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Immunology of Infectious Disease | Molecular Biology
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.
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Citation: Immunity. 2007 Aug;27(2):349-60. Link to article on publisher's site
Lim, Jae Hyang; Davis, Roger J.; and Li, Jian-Dong, "Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections" (2007). Davis Lab Publications. 60.