UVB-Induced Microvesicle Particle Release and Its Effects on the Cutaneous Microenvironment

Abstract

Ultraviolet B radiation (UVB) has profound effects on human skin that results in a broad spectrum of immunological local and systemic responses and is the major cause of skin carcinogenesis. One important area of study in photobiology is how UVB is translated into effector signals. As the skin is exposed to UVB light, subcellular microvesicle particles (MVP), a subtype of bioactive extracellular vesicles, are released causing a variety of local and systemic immunological effects. In this review, we highlight keratinocyte MVP release in keratinocytes in response to UVB. Specifically, Platelet-activating factor receptor agonists generated by UVB result in MVP released from keratinocytes. The downstream effects of MVP release include the ability of these subcellular particles to transport agents including the glycerophosphocholine-derived lipid mediator Platelet-activating factor (PAF). Moreover, even though UVB is only absorbed in the epidermis, it appears that PAF release from MVPs also mediates systemic immunosuppression and enhances tumor growth and metastasis. Tumor cells expressing PAF receptors can use this mechanism to evade chemotherapy responses, leading to treatment resistance for advanced cancers such as melanoma. Furthermore, novel pharmacological agents provide greater insight into the UVB-induced immune response pathway and a potential target for pharmacological intervention. This review outlines the need to more clearly elucidate the mechanism linking UVB-irradiation with the cutaneous immune response and its pathological manifestations. An improved understanding of this process can result in new insights and treatment strategies for UVB-related disorders from carcinogenesis to photosensitivity.

Platelet‐activating factor and microvesicle particles as potential mediators for the toxicity associated with intoxicated thermal burn injury

“…The formation of PAF and PAFR agonists then allows for their binding with PAFR, a G protein‐coupled receptor, which increases calcium levels and activates mitogen‐activated protein kinases (MAPK). LPCAT2 is phosphorylated by MAPK, leading to a positive feedback loop that continually generates high levels of PAF 21 . Thus, inflammatory cells that express high levels of LPCAT2 will yield very high quantities of PAF.…”

“…The use of pharmacologic inhibitors and knockout mice has indicated that the formation of MVP in response to many stimuli appears to be dependent on the translocation of the enzyme aSMase to the plasma membrane 17,33,38 . The initial step of MVP formation, the restructuring of the plasma membrane at the site of MVP production, has not yet been fully established, but the consequent components of the MVP gathering bioactive molecules and then budding and release of the MVP from the plasma membrane are dependent on aSMase 21,39,40 . The release of MVP which contain PAF and PAFR agonists proliferates PAFR activation throughout other cells, leading to PAF mediated systemic toxicity as a result of keratinocyte damage 30 .…”

“…LPCAT2 is phosphorylated by MAPK, leading to a positive feedback loop that continually generates high levels of PAF. 21 Thus, inflammatory cells that express high levels of LPCAT2 will yield very high quantities of PAF.…”

Regulation of Extracellular Vesicle-Mediated Immune Responses against Antigen-Specific Presentation

“…Extracellular vesicles (EVs) are lipid bilayer structures secreted by living cells and are classified into either exosomes, microvesicles (MVs), or apoptotic bodies, based on the intracellular production mechanism and size ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , …”

Scutellaria baicalensis Georgi regulates REV-ERBα/BMAL1 to protect against skin aging in mice

“…UV radiation is a major cause of photoaging, and can be divided into three bands [i.e., UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm)]. Of note, UVB is the predominant form that causes injuries to living organisms (Slominski et al, 2018a;Frommeyer et al, 2022). UV radiation not only induces skin pathology, but also exert systemic effects, including activation of hypothalamicpituitary-adrenal axis, opioidogenic effects, and immunosuppression.…”