Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective

Author(s)

Falcao-Holanda, Renata Brito ^[1] ; Karina Colo, Brunialti Milena ^[1] ; Jasiulionis, Miriam Galvonas ^[2] ; Salomao, Reinaldo ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Div Infect Dis, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pharmacol, Sao Paulo - Brazil

• Document type: Review article
• Source: FRONTIERS IN MEDICINE; v. 8, JUL 12 2021.
• Web of Science Citations: 0

Abstract

Sepsis is characterized by an initial hyperinflammatory response, with intense cell activation and cytokine storm. In parallel, a prolonged compensatory anti-inflammatory response, known as immunological tolerance, can lead to immunosuppression. Clinically, this condition is associated with multiple organ failure, resulting in the patient's death. The mechanisms underlying the pathophysiology of sepsis are not yet fully understood, but evidence is strong showing that epigenetic changes, including DNA methylation and post-translational modifications of histones, modulate the inflammatory response of sepsis. During the onset of infection, host cells undergo epigenetic changes that favor pathogen survival. Besides, epigenetic changes in essential genes also orchestrate the patient's inflammatory response. In this review, we gathered studies on sepsis and epigenetics to show the central role of epigenetic mechanisms in various aspects of the pathogenesis of sepsis and the potential of epigenetic interventions for its treatment. (AU)

• FAPESP's process: 17/21052-0 - Sepsis: mechanisms, therapeutic targets and epidemiology
• Grantee: Reinaldo Salomão
• Support Opportunities: Research Projects - Thematic Grants