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Therapeutic Targeting of NF-κB in Acute Lung Injury: A Double-Edged Sword.
Millar, Michelle Warren; Fazal, Fabeha; Rahman, Arshad.
  • Millar MW; Department of Pediatrics (Neonatology), Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
  • Fazal F; Department of Pediatrics (Neonatology), Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
  • Rahman A; Department of Pediatrics (Neonatology), Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Cells ; 11(20)2022 10 21.
Article in English | MEDLINE | ID: covidwho-2154904
ABSTRACT
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a devastating disease that can be caused by a variety of conditions including pneumonia, sepsis, trauma, and most recently, COVID-19. Although our understanding of the mechanisms of ALI/ARDS pathogenesis and resolution has considerably increased in recent years, the mortality rate remains unacceptably high (~40%), primarily due to the lack of effective therapies for ALI/ARDS. Dysregulated inflammation, as characterized by massive infiltration of polymorphonuclear leukocytes (PMNs) into the airspace and the associated damage of the capillary-alveolar barrier leading to pulmonary edema and hypoxemia, is a major hallmark of ALI/ARDS. Endothelial cells (ECs), the inner lining of blood vessels, are important cellular orchestrators of PMN infiltration in the lung. Nuclear factor-kappa B (NF-κB) plays an essential role in rendering the endothelium permissive for PMN adhesion and transmigration to reach the inflammatory site. Thus, targeting NF-κB in the endothelium provides an attractive approach to mitigate PMN-mediated vascular injury, not only in ALI/ARDS, but in other inflammatory diseases as well in which EC dysfunction is a major pathogenic mechanism. This review discusses the role and regulation of NF-κB in the context of EC inflammation and evaluates the potential and problems of targeting it as a therapy for ALI/ARDS.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Acute Lung Injury / COVID-19 Type of study: Experimental Studies Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Cells11203317

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Acute Lung Injury / COVID-19 Type of study: Experimental Studies Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Cells11203317