Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia.
Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia.
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DOI：
10.1111/j.1474-9726.2011.00720.x
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发表时间：
2011-10
期刊：
影响因子：
7.8
通讯作者：
Orihuela CJ
中科院分区：
文献类型：
--
作者：
Shivshankar P;Boyd AR;Le Saux CJ;Yeh IT;Orihuela CJ
Cellular senescence is an age-associated phenomenon that promotes tumor invasiveness due to the secretion of pro-inflammatory cytokines, proteases, and growth factors. Herein we demonstrate that cellular senescence also potentially increases susceptibility to bacterial pneumonia caused by Streptococcus pneumoniae (the pneumococcus), the leading cause of infectious death in the elderly. Aged mice had increased lung inflammation as determined by cytokine analysis and histopathology of lung sections. Immunoblotting for p16, pRb, and mH2A showed that elderly humans and aged mice had increased levels of these senescence markers in their lungs versus young controls. Keratin 10 (K10), Laminin Receptor (LR), and Platelet activating factor receptor (PAFr), host proteins known to be co-opted for bacterial adhesion, were also increased. Aged mice were found to be highly susceptible to pneumococcal challenge in a PsrP, the pneumococcal adhesin that binds K10, dependent manner. In vitro senescent A549 lung epithelial cells had elevated K10 and LR protein levels and were up to 5-fold more permissive for bacterial adhesion. Additionally, exposure of normal cells to conditioned media from senescent cells doubled PAFr levels and pneumococcal adherence. Genotoxic stress induced by bleomycin and oxidative stress enhanced susceptibility of young mice to pneumonia and was positively correlated with enhanced p16, inflammation, and LR levels. These findings suggest that cellular senescence facilitates bacterial adhesion to cells in the lungs and provides an additional molecular mechanism for the increased incidence of community-acquired pneumonia in the elderly. This study is the first to suggest a second negative consequence for the senescence-associated secretory phenotype.
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DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
3.1
作者：
Obert, Caroline;Sublett, Jack;Orihuela, Carlos J.
通讯作者：
Orihuela, Carlos J.
影响因子：
168.9
作者：
Lopez, Alan D.;Mathers, Colin D.;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.
影响因子：
14.9
作者：
Garcia, Christine Kim;Wright, Woodring E;Shay, Jerry W
通讯作者：
Shay, Jerry W