UVB‐generated Microvesicle Particles: A Novel Pathway by Which a Skin‐specific Stimulus Could Exert Systemic Effects

Abstract

Ultraviolet B radiation (UVB) exerts profound effects on human skin. Much is known regarding the ability of UVB to generate a plethora of bioactive agents ranging from cytokines and other bioactive proteins, lipid mediators and micro-RNAs. It is presumed that these agents are in large part responsible for the effects of UVB, which only is absorbed appreciably in the epidermis. However, the exact mechanism by which these bioactive agents can leave the epidermis are as yet unclear. This review addresses the potential role of microvesicle particles (MVP) as UVB signaling agents through transmitting biologic mediators. New data is provided that UVB treatment of human skin explants also generates MVP production. We hypothesize that UVB production of MVPs (UVB-MVP) could serve this important function of transmitting keratinocyte-derived bioactive agents. Moreover, we propose that UVB-MVP formation involves the lipid mediator Platelet-activating factor. This novel pathway has the potential to be exploited pharmacologically to modulate UVB effects.

Gemcitabine Induces Microvesicle Particle Release in a Platelet-Activating Factor-Receptor-Dependent Manner via Modulation of the MAPK Pathway in Pancreatic Cancer Cells

“…These findings indicate the potential role of the PAF-R in gemcitabine-mediated MVP release. These findings further characterized, and defined, the role of cellular PAF-R in MVP release in response to stimuli similar to, as described [16,17]. Since, we did not observe a dose-dependent effect of gemcitabine on MVP release (Figure 2A), and we chose 0.1 mM dose of gemcitabine for our next experiments.…”

“…Multiple studies have demonstrated that MVPs contain bioactive components, including lipids [16,17,18]. As therapeutic agents, including chemotherapeutic agents, generate PAF-R agonists from tumor cells [6,7], we next tested if MVPs released by gemcitabine contain PAF-R agonists.…”

“…Growing evidence supports the crucial roles of microvesicle particles (MVPs), an extracellular vesicles in mediating the biological activities of cells in response to stimuli, including cancer therapy [12,13,14,15]. MVPs are small membrane-bound nanosized (10–100 nm) particles which are released by various cell types, including tumor cells, and contain a variety of bioactive substances, including lipids [14,15,16,17,18]. Thus, ongoing efforts are directed toward defining the functional role, as well as mechanisms of MVPs in disease pathophysiologies, including cancers, to devise better therapeutic strategies against these ailments.…”

“…The recent reports from our group have demonstrated that PAF-agonists generated in response to the environmental stressor, ultraviolet B (UVB), are extracellularly transported via MVP [16,17]. Notably, UVB exposure resulted in MVP release in a dose-dependent manner from PAF-R-expressing human keratinocyte HaCaT cells, and human skin explants [16,17]. This UVB-induced effect on MVP release is mimicked by a known PAF-R agonist, carbamoyl-PAF (CPAF) [17].…”

Enhanced Platelet-Activating Factor Synthesis Facilitates Acute and Delayed Effects of Ethanol-Intoxicated Thermal Burn Injury

“…De-identified skin was obtained from contouring surgery (abdominoplasty and brachioplasty) (Fahy et al, 2017;Travers et al, 2010). Patient consent for experiments was not required because our institutions consider de-identified human tissue left over from surgery as discarded material and thus the studies were exempt.…”