Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 175, Issue 8, Pages 763-767Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200610-1436CP
Keywords
compartmentalization; epigenetic; gene silencing; reprogramming
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Funding
- NCRR NIH HHS [M0-1RR 007122] Funding Source: Medline
- NIAID NIH HHS [R01AI-09169, R01AI-065791] Funding Source: Medline
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This critical care perspective appraises reprogramming of gene expression in inflammatory diseases as an emerging concept of clinical importance. We emphasize gene reprogramming that silences acute proinflammatory genes during severe systemic inflammation, wherein in the systemic inflammatory response syndrome (SIRS) exists as a continuum during severe sepsis, septic shock, and the multiorgan dysfunction and failure phenotypes without infection. In contrast, silencing of acute proinflammatory genes is not apparent in sites of localized inflammatory processes like rheumatoid arthritis. We discuss in three parts the clinical context and the translational basic science associated with gene silencing during the SIRS continuum of severe systemic inflammation: (7) reprogramming of acute proinflammatory genes; (2) a nuclear factor-kappa B paradox, coupled with ReIB expression, that combine to silence genes using an epigenetic (inherited and reversible) signature on the nucleosome; and (3) the potential clinical importance of compartmentalization in gene silencing. Our emergent understanding of these physiologic processes may provide a novel framework for developing treatments.
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