Cigarette smoke triggers code red: p21CIP1/WAF1/SDI1 switches on danger responses in the lung.
The article by Yao and coworkers in this issue (Am. J. Respir. Cell Mol. Biol. 2008;39:7-18) reveals that the cyclin-dependent kinase inhibitor p21CIP1/WAF1/SDI1 (designated hereafter as p21), which has been linked to cell cycle growth arrest due to stress or danger cell responses, may modulate alveolar inflammation and alveolar destruction, and thus enlightens our present understanding of how the lung senses injury due to cigarette smoke and integrates these responses with those that activate inflammatory pathways potentially harmful to the lung. Furthermore, the interplay of p21 and cellular processes involving cell senescence and the imbalance of cell proliferation/apoptosis may provide us with a more logical explanation of how p21, acting as a sensor of cellular stress, might have such potent and wide roles in lung responses triggered by cigarette smoke. Molecular switches, ontologically designed for the protection of the host, are now hijacked by injurious stresses (such as cigarette smoke), leading to organ damage.
Tuder
Rubin M
RM
Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, 4200 East 9th Avenue, Campus Box C272, Denver, CO 80262, USA. Rubin.Tuder@UCHSC.EDU
Yun
Jeong H
JH
Graham
Brian B
BB
D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000172:deficiency / Q000378:metabolism*; D004646:Emphysema / Q000503:physiopathology; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000254:growth & development / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects*; D016615:Telomere / Q000502:physiology
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008070:Lipopolysaccharides; D009240:N-Formylmethionine Leucyl-Phenylalanine