Burn Injury: Mechanisms of Keratinocyte Cell Death

Abstract

Cutaneous burn injury is associated with epidermal loss in the zone of coagulation zone and delayed tissue loss in the zone of stasis. Thus, thermal stress can trigger both necrosis and regulated cell death (RCD) or apoptosis. Experimental in vitro and in vivo work has clearly demonstrated apoptotic events of thermally injured keratinocytes that are accompanied by morphological and biochemical markers of regulated cell death. However, in vivo data for the different pathways of regulated cell death are sparse. In vitro experiments with heat-stressed human keratinocytes have demonstrated death receptor involvement (extrinsic apoptosis), calcium influx, and disruption of mitochondrial membrane potential (intrinsic apoptosis) in regulated cell death. In addition, caspase-independent pathways have been suggested in regulated cell death. Keratinocyte heat stress leads to reduced proliferation, possibly as a result of reduced keratinocyte adhesion (anoikis) or oncogene involvement. Understanding the underlying mechanisms of RCD and the skin’s responses to thermal stress may lead to improved strategies for treating cutaneous burn trauma.

Effects of 445 nm, 520 nm, and 638 nm Laser Irradiation on the Dermal Cells

“…In keratinocytes exposed to high fluences of 638 nm red light irradiation, we also observed decreased viability and proliferation rates compared to sham exposed cells. Again, the observed changes are consistent with the effects of heat stress [ 36 ]. However, low fluences (13.8 and 41.3 J/cm 2 ) of 638 nm irradiation significantly induced the proliferation rate of Ker-CT cells.…”

The Yin and Yang dualistic features of autophagy in thermal burn wound healing

“…Recent studies revealed that in case of burns, cell death may occur due to necrosis, autophagy, and apoptosis, all leading through a specific molecular path to burn injury positive or negative evolution. 109 – 112 …”

“…Necroptosis, necrosis, and secondary necrosis following apoptosis have been recently highlighted as different mechanisms of cell death. 109 – 112 These mechanisms are based on similar cellular and molecular events: redox imbalance, oxidative burst, hyperpolarization of the mitochondrial membrane, and permeation of lysosomal membrane, and of the cell membrane. 109 – 112 …”

“… 109 – 112 These mechanisms are based on similar cellular and molecular events: redox imbalance, oxidative burst, hyperpolarization of the mitochondrial membrane, and permeation of lysosomal membrane, and of the cell membrane. 109 – 112 …”

“…Necrosis is considered an accidental type of cell death, occurring as a response to severe cell damages, like those occurred in the first moments of thermic burns. 109 – 112 The necrotic cell death molecular mechanism can be finely orchestrated by specific signal transduction pathways, involving both the receptor interaction protein kinase 1 and 3 (RIP1 and RIP3). 113 Catabolic processes (necroptosis) also play important roles on cellular necrosis stage.…”