Modulation of Bcl‐2 Proteins in an in Vitro Model of Sepsis

Abstract

Bcl‐2 family proteins regulate mitochondrial apoptosis and have been shown to be involved in a variety of diseases. In sepsis, systemic inflammatory response to pathogens, apoptosis is triggered in immune cells as a result of the cytokine storm induced by sepsis. Immune cell death is not the only damage caused by sepsis and the mechanism of cellular injury on end organs is unknown despite advances in modern medicine. Much of the mortality associated with sepsis is a result of end organ failure, particularly the kidneys. Research has shown that a small amount of apoptotic cell death is characteristic in acute renal injury associated with sepsis, thus Bcl‐2 family proteins should be involved in renal death as a result of septic shock. Use of a two‐step cell culture model stresses immune cells to stimulate cytokine release comparable to the cytokine storm found in sepsis, which can then be harvested and used to treat cultured kidney cells to induce death. Examination of Bcl‐2 proteins after treatment with stimulated cytokines showed a decrease in cell viability; an increase of BH3 only, pro‐apoptotic proteins; and a decrease in anti‐apoptotic Bcl‐2 confirming their hypothesized involvement. Results provide hope for elucidation of the mechanism of sepsis from which more efficient treatments can be developed. Research funded by Elon University URP, Department of Chemistry, Elon College Fellows, and the Provost Award to VDGM.