ALTERED LEVELS OF H3K9AC, H3K4ME3, AND H3K27ME3 IN PROMOTERS OF DIFFERENTIALLY EXPRESSED GENES RELATED TO INNATE IMMUNE RESPONSE IN SEPTIC PATIENTS WITH DIFFERENT CLINICAL OUTCOMES.

Sepsis is one of the leading causes of morbidity and mortality worldwide. Monocytes seem to undergo functional reprogramming during sepsis, resulting in dysregulated host immune response. To clarify this dysregulation mechanism, we investigated three histone modifications found in promoters of genes involved in innate immune response, and associated these findings with gene transcription in septic patients.

Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective.

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.

TLR4 deficiency upregulates TLR9 expression and enhances irinotecan-related intestinal mucositis and late-onset diarrhoea.

Background And Purpose: Severe diarrhoea, a common gastrointestinal manifestation of anticancer treatment with irinotecan, might involve single nucleotide polymorphisms (SNPs) of toll-like receptors (TLRs), described as critical bacterial sensors in the gut. Here, colorectal cancer patients carrying missense TLR4 A896G (rs4986790) or C1,196T (rs4986791) SNPs and Tlr4 knockout (Tlr4-/-) mice were given irinotecan to investigate the severity of the induced diarrhoea.

Experimental Approach: Forty-six patients treated with irinotecan-based regimens had diarrhoea severity analysed according to TLR4 genotypes.