A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis

Abstract

Chronic wounds show necroptosis from which keratinocytes must be protected to enable appropriate wound re-epithelialization and closure. Poloxamers, a class of synthetic triblock copolymers, are known to be effective against plasma membrane damage (PMD). The purpose of this study is to evaluate the efficacy of a specific poloxamer, surfactant polymer dressing (SPD), which is currently used clinically as wound care dressing, against PMD in keratinocytes. Triton X-100 (TX100) at sub-lytic concentrations caused PMD as demonstrated by the efflux of calcein and by the influx of propidium iodide and FM1-43. TX100, an inducer of necroptosis, led to mitochondrial fragmentation, depletion of nuclear HMGB1, and activation of signaling complex associated with necroptosis (i.e., activation of RIP3 and phosphorylation of MLKL). All responses following exposure of human keratinocytes to TX100 were attenuated by pre- or co-treatment with SPD (100 mg/ml). The activation and translocation of phospho-MLKL to the plasma membrane, taken together with depletion of nuclear HMGB1, characterized the observed cell death as necroptosis. Thus, our findings show that TX100-induced plasma membrane damage and death by necroptosis were both attenuated by SPD, allowing keratinocyte survival. The significance of such protective effects of SPD on keratinocytes in wound re-epithelialization and closure warrant further studies.

Non-Ionic Surfactants for Stabilization of Polymeric Nanoparticles for Biomedical Uses

“…Currently, it highlights the trend of surfactant therapies to lessen alterations in surface tension derived from inflammatory processes. However, the levels of industrial surfactants in the environment have always been a matter of concern and monitoring [9][10][11]. Current applications of surfactants in the manufacture of NP for biomedical applications seek a vectorization phenomenon to facilitate drug release at receptor sites [12].…”

Examination of the role of necroptotic damage-associated molecular patterns in tissue fibrosis

“…Due to tissue specificity, different DAMPs are released from distinct tissue when they undergo necroptosis. In skin-related fibrosis diseases, HMGB1 binds to TLR2 and TLR4 to stimulate the release of TNF, IL-1, IL-6, and IL-8, which increases the expression of α-SMA and collagen I in epidermal cells, keratinocytes, and dermal fibroblasts, thus forming hypertrophic scar ( 24 , 25 ). Fibronectin-EDA and tenascin-C combine with TLR4 to increase the expression of TGF-β, TIMP-1, and collagens in myofibroblasts and plasmacytoid dendritic cells, thus inducing epidermal fibrosis and sclerosis.…”

Myo‐Inositol in Fermented Sugar Matrix Improves Human Macrophage Function

“…Signal was visualized by subsequent incubation with fluorescence-tagged secondary antibodies followed by counterstaining with DAPI. [94][95][96] Images were captured by Axioscanner microscope. Confocal microscopy was performed on a Zeiss LSM 880 microscope equipped with the AIRYscan detector.…”

“…Confocal microscopy was performed on a Zeiss LSM 880 microscope equipped with the AIRYscan detector. [95,97] Quantification of fluorescent intensity of image was performed using ZenBlue v3.1 (Zeiss, Germany) software.…”