Thermal injuries cause severe damage on the cellular and tissue level and are considered especially challenging in the clinical routine. Complex interactions of different cell types and pathways dictate the formation of burn wounds. Thus, complications like burn wound progression, where so far viable tissue becomes necrotic and the size and depth of the wound increases, are difficult to explain, mainly due to the lack of simple model systems. We tested the behavior of human fibroblasts after heat treatment. A prominent response of the cells is to activate the heat shock response (HSR), which is one of the primary emergency mechanisms of the cell to proteotoxic stress factors such as heat. However, after a powerful but not lethal heat shock we observed a delayed activation of the HSR. Extending this model system, we further investigated these static cells and observed the emergence of senescent cells. In particular, the cells became β-galactosidase positive, increased p16 levels and developed a senescence-associated secretory phenotype (SASP). The secretion of cytokines like IL-6 is reminiscent of burn wounds and generates a bystander effect in so far non-senescent cells. In agreement with burn wounds, a wave of cytokine secretion enhanced by invading immune cells could explain complications like burn wound progression. A simple cell culture model can thus be applied for the analysis of highly complex conditions in human tissues.
Keywords: Burn wound progression; Burn wounds; Heat shock response; In vitro model; Senescence.
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