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.
Highlights
Sepsis is a syndrome that includes different abnormalities, described in 1992 as systemic inflammatory response syndrome
It was believed that its pathogenesis was mainly due to an unbalanced inflammatory response of the organism triggered by the presence of an infectious agent
These include Toll-like receptors (TLRs), cytosolic RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs), which induce complex intracellular signaling with complementary activities that activate transcriptional factors that regulate inflammatory response genes, generating dynamic changes in chromatin [26, 29,30,31]
Summary
Sepsis is a syndrome that includes different abnormalities, described in 1992 as systemic inflammatory response syndrome. The host innate immune system cells release an excessive number of inflammatory mediators through recognizing the pathogen by pattern recognition receptors (PRRs) that identify the microorganism through pathogenassociated molecular patterns (PAMPs) and damages (DAMPs) These include Toll-like receptors (TLRs), cytosolic RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs), which induce complex intracellular signaling with complementary activities that activate transcriptional factors that regulate inflammatory response genes, generating dynamic changes in chromatin [26, 29,30,31]. Several cellular metabolites can activate or inhibit different enzymes involved in epigenetic programming They induce changes in chromatin and DNA, modulate gene transcription, and lead to different functional states during sepsis, such as excessive inflammation immunoparalysis [2, 33]. Exposure to LPS increases the stability of CBP by reducing interaction with the FBXL19 subunit of ubiquitin ligase 3 and activating the deubiquitylating enzyme
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
