Inflammasome Activation of IL‐1 Family Mediators in Response to Cutaneous Photodamage^†

Abstract

Although keratinocytes are relatively resistant to ultraviolet radiation (UVR) induced damage, repeated UVR exposure result in accumulated DNA mutations that can lead to epidermal malignancies. Keratinocytes play a central role in elaborating innate responses that lead to inflammation and influence the generation of adaptive immune responses in skin. Apart from the minor cellular constituents of the epidermis, specifically Langerhans cells and melanocytes, keratinocytes are the major source of cytokines. UVR exposure stimulates keratinocytes to secrete abundant pro-inflammatory IL-1-family proteins, IL-1α, IL-1β, IL-18 and IL-33. Normal skin contains only low levels of inactive precursor forms of IL-1β and IL-18, which require caspase 1-mediated proteolysis for their maturation and secretion. However, caspase-1 activation is not constitutive, but dependents on the UV-induced formation of an active inflammasome complex. IL-1 family cytokines can induce a secondary cascade of mediators and cytokines from keratinocytes and other cells resulting in wide range of innate processes including infiltration of inflammatory leukocytes, induction of immunosuppression, DNA repair or apoptosis. Thus, the ability of keratinocytes to produce a wide repertoire of proinflammatory cytokines can influence the immune response locally as well as systematically, and alter the host response to photodamaged cells. We will highlight differential roles played by each IL-1 family molecule generated by UV-damaged keratinocytes, and reveal their complementary influences in modulating acute inflammatory and immunological events that follow cutaneous UV exposure.

Identification and validation of biomarkers associated with acute and chronic graft versus host disease

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Systemic Response to Ultraviolet Radiation Involves Induction of Leukocytic IL-1β and Inflammation in Zebrafish

“…We show that upon UV exposure, leukocytes become activated and contribute toward inflammation by elevating IL-1b. Innate immune responses to UV exposure have been studied mainly in vitro in keratinocyte cultures (33). The initial response of keratinocytes includes inflammasome formation, resulting in activation of proinflammatory cytokines (34).…”

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“…Other than solid inanimate surfaces, human cells in wounds may be damaged by UV irradiation, particularly in the wavelength range of 180-400 nm [25,32,33,34]. At high doses, UV radiation may not only cause cell damage and lead to apoptosis but may also induce cancer [35].…”