Mechanical deformation promotes secretion of IL-1 alpha and IL-1 receptor antagonist.

Abstract

Both IL-1 alpha and IL-1 beta lack an N terminus secretory sequence, and the mechanism of secretion of these pleiotropic cytokines is incompletely understood. The epidermis contains large quantities of IL-1 alpha in keratinocytes, which may play a role in inducing endothelial adhesion molecules and promoting extravasation of leukocytes. Here we report that mechanical deformation of human keratinocytes leads to rapid release of IL-1 alpha, possibly through transient disruptions in the plasma membrane. Using a device that precisely controls the amplitude of strain on the culture substrate, we found by pulse-chase analysis, Western analysis, and ELISA that the release of IL-1 alpha is dependent on the amplitude of the strain. A cyclic strain of 14% released a small but significant quantity of IL-1 alpha, while strains of 33% released 66 +/- 9% of cytoplasmic IL-1 alpha over 1 h (p < 0.001). Release of IL-1 alpha was accompanied by rapid release of large stores of IL-1R antagonist, approximately 25 to 30 times greater by mass than the quantity of IL-1 alpha released, but only a small fraction of cytoplasmic lactate dehydrogenase. Media conditioned by mechanically stimulated keratinocytes induced expression of E-selectin by human vascular endothelial cells; induction of E-selectin was completely inhibited by an Ab to IL-1 alpha. Therefore, mechanical strain promotes the secretion of IL-1 alpha, and deformation of keratinocytes in the epidermis may activate vascular endothelium through mechanically released IL-1 alpha. This pathophysiologic mechanism may play a role in the anatomic localization of some inflammatory skin diseases, such as psoriasis, which occurs more commonly in locations where the dermis is subjected to repetitive stretch or trauma.

Investigating the Early Events after Skin-Barrier Disruption Using Microdialysis—A Human Ex Vivo Skin Model

“…VEGF is known to play a role in the later angiogenic phase of wound healing, but there are several studies showing an immediate secretion of the growth factor as a consequence of skin-barrier disruption [33][34][35], which is corroborated by the present study. The proinflammatory cytokine IL-1α is prestored in keratinocytes and serves as an acute damage signal [36,37]. This is reflected by the increasing dialysate concentrations of IL-1α observed in this study after mechanical disruption of the skin barrier.…”

Injury-induced interleukin-1 alpha promotes Lgr5 hair follicle stem cells de novo regeneration and proliferation via regulating regenerative microenvironment in mice

“…Generally, IL-1α is particularly abundant in the cytokine profile of activated macrophages, neutrophils, epithelial cells, and endothelial cells. Keratinocytes, in particular, release large amounts of IL-1α following tissue injury or stress-related stimuli [ 51 , 52 ]. The transcription factors AP1 and NF-κB can also induce IL-1α expression in a cell-type-specific manner [ 53 – 55 ].…”

Inflammatory biomarkers in sebum for identifying skin damage in patients with a Stage I pressure ulcer in the pelvic region: A single centre observational, longitudinal cohort study with elderly patients

“…However, with the use of the new extraction protocol, we were able to quantify low‐abundant cytokines, such as IL‐8 and G‐CSF that could provide a classification of damaged skin from healthy skin 22 . It is well known that a variety of skin insults (mechanical, chemical and thermal) alters the production of the high‐abundant cytokines, namely, IL‐1α and IL‐1RA 12 . In addition, each of the low‐abundant cytokines plays a unique role in maintaining the barrier function, for example, TNF‐α, INF‐γ and IL‐1β are important in lipid synthesis, whereas IL‐8 and G‐CSF are associated with dendritic cell migration and neutrophil regulation 35‐37 .…”

“…Keratinocytes in the skin layer play a major role in the inflammatory processes by the production of signalling molecules, namely, cytokines and chemokines. Previous in‐vitro studies, involving cell and tissue models, and animal studies have reported the release of cytokines following prolonged mechanical loading 12,13 . Non‐invasive adhesive tapes have been used to sample cytokines typically IL‐1α, IL‐1RA, IL‐8, INF‐γ, and IL‐6 from sebum on the skin surface.…”

“…Previous in-vitro studies, involving cell and tissue models, and animal studies have reported the release of cytokines following prolonged mechanical loading. 12,13 Non-invasive adhesive tapes have been used to sample cytokines typically IL-1α, IL-1RA, IL-8, INF-γ, and IL-6 from sebum on the skin surface. Subsequently, studies have shown their upregulation following prescribed mechanical and chemical insults, [14][15][16][17] as well as clinically relevant loads following the attachment of medical devices.…”