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

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.

• Publication year

  1997

• Venue

  Journal of Immunology

• Publication date

  1997-11-15

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.4049/jimmunol.159.10.5084PMID 9366437
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues

  1997cited by this paper
• Mechanical strain tightly controls fibroblast growth factor-2 release from cultured human vascular smooth muscle cells.

  1997cited by this paper
• Barrier disruption stimulates interleukin-1 alpha expression and release from a pre-formed pool in murine epidermis.

  1996cited by this paper
• Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis.

  1995cited by this paper
• Interleukin-1β Secretion. A POSSIBLE MULTISTEP PROCESS THAT IS REGULATED IN A CELL TYPE-SPECIFIC MANNER (*)

  1995cited by this paper
• Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.

  1995cited by this paper
• Interleukin-1 receptor antagonist.

  1995cited by this paper
• Distinct cell surface ligands mediate T lymphocyte attachment and rolling on P and E selectin under physiological flow

  1994cited by this paper
• E-selectin and vascular cell adhesion molecule-1 are critical for initial trafficking of helper-inducer/memory T cells in psoriatic plaques.

  1994cited by this paper
• Device for the application of a dynamic biaxially uniform and isotropic strain to a flexible cell culture membrane

  1994cited by this paper
• Structure and mechanism of interleukin-1 beta converting enzyme.

  1994cited by this paper
• Skin disease‐related T cells bind to endothelial selectins: expression of cutaneous lymphocyte antigen (CLA) predicts E‐selectin but not P‐selectin binding

  1994cited by this paper
• Three-dimensional structures of acidic and basic fibroblast growth factors.

  1993cited by this paper
• Interleukin 1: The patterns of translation and intracellular distribution support alternative secretory mechanisms

  1992cited by this paper
• Transient disruptions of aortic endothelial cell plasma membranes.

  1992cited by this paper
• Molecular cloning of the interleukin-1 beta converting enzyme.

  1992cited by this paper
• cDNA cloning of an intracellular form of the human interleukin 1 receptor antagonist associated with epithelium.

  1991cited by this paper
• ELAM-1 is an adhesion molecule for skin-homing T cells

  1991cited by this paper
• Interleukin 1 receptor antagonist. A new member of the interleukin 1 family.

  1991cited by this paper
• Interleukin 1 is processed and released during apoptosis.

  1991cited by this paper
• Interleukin 1 receptor antagonist in human epidermis and cultured keratinocytes

  1991cited by this paper
• Basic fibroblast growth factor is efficiently released from a cytolsolic storage site through plasma membrane disruptions of endothelial cells

  1991cited by this paper
• IL-1 secretion by macrophages. Enhancement of IL-1 secretion and processing by calcium ionophores.

  1990cited by this paper
• Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein

  1990cited by this paper
• Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations.

  1990cited by this paper
• Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist.

  1990cited by this paper
• Gastrointestinal cell plasma membrane wounding and resealing in vivo.

  1989cited by this paper
• The heparin-binding (fibroblast) growth factor family of proteins.

  1989cited by this paper
• Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells.

  1986cited by this paper
• Interleukin 1 is present in normal human epidermis.

  1986cited by this paper

• Endurance Athletes and Skin Aging: Mechanisms, Risks, and Protective Strategies

  2025cites this paper
• HLA-B*57:01-dependent intracellular stress in keratinocytes triggers dermal hypersensitivity reactions to abacavir

  2024cites this paper
• 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

  2023influential citation
• Injury-induced interleukin-1 alpha promotes Lgr5 hair follicle stem cells de novo regeneration and proliferation via regulating regenerative microenvironment in mice

  2023cites this paper
• Kinetic Characterization of the Immune Response to Methicillin-Resistant Staphylococcus aureus Subcutaneous Skin Infection

  2022cites this paper
• Loricrin at the Boundary between Inside and Outside

  2022cites this paper
• The Role of KEAP1-NRF2 System in Atopic Dermatitis and Psoriasis

  2022cites this paper
• Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging

  2021cites this paper
• The Relevance of IL-1-Signaling in the Protection against Gram-Positive Bacteria

  2021cites this paper
• The Epidermis: Redox Governor of Health and Diseases

  2021cites this paper
• Investigating the Early Events after Skin-Barrier Disruption Using Microdialysis—A Human Ex Vivo Skin Model

  2021cites this paper
• Effect of 1-MHz ultrasound on the proinflammatory interleukin-6 secretion in human keratinocytes

  2021cites this paper
• Electrospun fibers enhanced the paracrine signaling of mesenchymal stem cells for cartilage regeneration

  2021influential citation
• Cytokinocytes: the diverse contribution of keratinocytes to immune responses in skin

  2020cites this paper
• Comparing the effects of three different multilayer dressings for pressure ulcer prevention on sacral skin after prolonged loading: An exploratory crossover trial

  2020cites this paper
• Intracellular IL-1 Receptor Antagonist Isoform 1 Released from Keratinocytes upon Cell Death Acts as an Inhibitor for the Alarmin IL-1α

  2020cites this paper
• Pathogenic implication of epidermal scratch injury in psoriasis and atopic dermatitis

  2020cites this paper
• The Effect of Shear Force on Skin Viability in Patients with Type 2 Diabetes

  2019cites this paper
• New insights in the development of pressure ulcers

  2019cites this paper
• Characterization of Cytokines and Proliferation Marker Ki67 in Cleft Affected Lip Tissue

  2019cites this paper
• Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes

  2019cites this paper
• Androgenic alopecia and dutasteride in hair mesotherapy: A short review

  2018cites this paper
• Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of γδT-cells

  2017influential citation
• Inducible lymphoid clusters, iSALTs, in contact dermatitis: a new concept of acquired cutaneous immune responses

  2016cites this paper
• Improving the effect of shear on skin viability with wound dressings.

  2016cites this paper
• Biologics in Staphylococcus aureus arthritis

  2016cites this paper
• Kinetic factors may trigger lesion development in the patients with psoriatic arthritis

  2016cites this paper
• Investigation of Human Embryonic Stem Cell-Derived Keratinocytes as an In Vitro Research Model for Mechanical Stress Dynamic Response

  2015cites this paper
• Investigating the molecular basis for resistance to the sea louse, Lepeophtheirus salmonis, among salmonids

  2015cites this paper
• Improving spineboard design

  2015cites this paper
• Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus

  2014cites this paper
• The effect of narrow-band ultraviolet-B phototherapy on soluble intercellular adhesion molecule-1 and soluble E-selectin in psoriasis vulgaris patients

  2014cites this paper
• Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin

  2014cites this paper
• Oxidative Conditioning and Treatment for Osteoarthritis

  2013cites this paper
• Antimicrobial Response to Dramatically Enhance the Epidermal By IL-1 Signaling, Monocyte-Derived Cells

  2013cites this paper
• Place de l'Interleukine-33 dans la réponse immune du foie au cours de la leishmaniose viscérale

  2013cites this paper
• Interleukin 33 as a Mechanically Responsive Cytokine Secreted by Living Cells*

  2012cites this paper
• Mice deficient in hepatocyte‐specific IL‐1Ra show delayed resolution of concanavalin A‐induced hepatitis

  2012cites this paper
• Comparative defense-associated responses in salmon skin elicited by the ectoparasite Lepeophtheirus salmonis.

  2012cites this paper
• Development of Transgenic Cloned Pig Models of Skin Inflammation by DNA Transposon-Directed Ectopic Expression of Human β1 and α2 Integrin

  2012cites this paper
• Interleukin-33 and the function of innate lymphoid cells.

  2012cites this paper
• Noninvasive in vivo imaging to evaluate immune responses and antimicrobial therapy against Staphylococcus aureus and USA300 MRSA skin infections.

  2011cites this paper
• Novel role of caspase-8 in the maintenance of epidermal regeneration and repair

  2011cites this paper
• Articular inflammation is controlled by myeloid cell-derived interleukin 1 receptor antagonist during the acute phase of arthritis in mice

  2011cites this paper
• Augmentation of CCL17 and CCL28 gene expression by TNF-alpha, IL-1beta, or IFN-gamma in cultured canine keratinocytes.

  2010cites this paper
• Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate

  2010cites this paper
• Evidence for altered Wnt signaling in psoriatic skin.

  2010cites this paper
• Cytokine release in tissue-engineered epidermal equivalents after prolonged mechanical loading.

  2010cites this paper
• Neuroimmunology Of The Skin

  2009cites this paper
• Immune Circuits of the Skin

  2009cites this paper
• The Transport Profile of Cytokines in Epidermal Equivalents Subjected to Mechanical Loading

  2009cites this paper
• Inflammasome-mediated production of IL-1β is required for neutrophil recruitment against Staphylococcus aureus in vivo.

  2008cites this paper
• Application of a Systems Biology Approach to Skin Allergy Risk Assessment

  2008cites this paper
• Diffusion measurements in epidermal tissues with fluorescent recovery after photobleaching

  2008cites this paper
• Interleukin-1beta and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes: a possible explanation for oxidative stress generation.

  2008cites this paper
• Flagellin is the principal inducer of the antimicrobial peptide S100A7c (psoriasin) in human epidermal keratinocytes exposed to Escherichia coli

  2008cites this paper
• Cyclic tensile strain increases interactions between human epidermal keratinocytes and quantum dot nanoparticles.

  2008cites this paper
• Type I IL-1 receptor mediates IL-1 and intracellular IL-1 receptor antagonist effects in skin inflammation.

  2007cites this paper
• Cytokine and chemokine release upon prolonged mechanical loading of the epidermis

  2007cites this paper
• Biochemical markers for early detection of superficial pressure ulcers

  2007influential citation
• Roles of IL-1α in the Growth of Keratocystic Odontogenic Tumor

  2007cites this paper
• Effects of Mechanical Stimuli on Biological Interactions with Amino Acid-Derivatized Fullerenes at the Tissue and Cellular Levels

  2007cites this paper
• Biochemical marker for early and objective detection of grade 1 pressure ulcers

  2007cites this paper
• Mechanotransduction of keratinocytes in culture and in the epidermis.

  2007cites this paper
• Inflammasome-Mediated Production of IL-1β Is Required for Neutrophil Recruitment against Staphylococcus aureus In Vivo1

  2007cites this paper
• Modeled Repetitive Motion Strain and Indirect Osteopathic Manipulative Techniques in Regulation of Human Fibroblast Proliferation and Interleukin Secretion

  2007cites this paper
• Influence of interleukin‐1α on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells

  2006cites this paper
• Influence of interleukin-1alpha on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells.

  2006cites this paper
• Wound healing: immunological aspects.

  2006cites this paper
• Langerhans Cells and Skin Irritation

  2006cites this paper
• Psoriasis: skin and joints, same fight?

  2006cites this paper
• FK506 (Tacrolimus) Inhibition of Intracellular Production and Enhancement of Interleukin 1α through Glucocorticoid Application to Chemically Treated Human Keratinocytes

  2005cites this paper
• Pre-interleukin-1alpha expression reduces cell growth and increases interleukin-6 production in SaOS-2 osteosarcoma cells: Differential inhibitory effect of interleukin-1 receptor antagonist (icIL-1Ra1).

  2005cites this paper
• Understanding psoriatic arthritis.

  2005cites this paper
• Counter-regulation of interleukin-1alpha (IL-1alpha) and IL-1 receptor antagonist in murine keratinocytes.

  2005cites this paper
• Modeling the transport of biochemical markers in skin : towards pressure ulcer risk assessment

  2005influential citation
• Lipoprotein aggregation protects human monocyte-derived macrophages from OxLDL-induced cytotoxicity Published, JLR Papers in Press, March 16, 2005. DOI 10.1194/jlr.M400485-JLR200

  2005cites this paper
• Impact of Cutaneous IL-10 on Resident Epidermal Langerhans’ Cells and the Development of Polarized Immune Responses

  2005cites this paper
• Effects of Positive Pressure in Odontogenic Keratocysts

  2005influential citation
• Association of the risk of osteoarthritis with high innate production of interleukin-1beta and low innate production of interleukin-10 ex vivo, upon lipopolysaccharide stimulation.

  2005cites this paper
• Counter-Regulation of Interleukin-1α (IL-1α) and IL-1 Receptor Antagonist in Murine Keratinocytes

  2005cites this paper
• Membrane-Associated IL-1 Contributes to Chronic Synovitis and Cartilage Destruction in Human IL-1α Transgenic Mice

  2004cites this paper
• Pro-inflammatory cytokine IL-1alpha potential for tissue repair in chemically and mechanically induced injury in cultured human keratinocytes.

  2004cites this paper
• Relation between size of odontogenic jaw cysts and the pressure of fluid within.

  2004cites this paper
• Measurement of cytokine expression and Langerhans cell migration in human skin following suction blister formation

  2004cites this paper
• Comparative Immunology of the Integument

  2004cites this paper
• In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic scars

  2003cites this paper
• Gyrodactylus derjavini infection elicits IL-1beta expression in rainbow trout skin.

  2003cites this paper
• A role for the interleukin-1 receptor in the pathway linking static mechanical compression to decreased proteoglycan synthesis in surface articular cartilage.

  2003cites this paper
• Mechanobiology of force transduction in dermal tissue

  2003cites this paper
• CX-659S, a diaminouracil derivative, indirectly inhibits the function of Langerhans cells by blocking the MEK1/2-Erk1/2 pathway in keratinocytes.

  2003cites this paper
• Intracellular Interleukin-1 Receptor Antagonist in Osteoarthritis Chondrocytes

  2003cites this paper
• Regulation of Interleukin-1α Expression by Integrins and Epidermal Growth Factor Receptor in Keratinocytes from a Mouse Model of Inflammatory Skin Disease*

  2003cites this paper
• Transgenic Mice a in Human IL-1 Chronic Synovitis and Cartilage Destruction Membrane-Associated IL-1 Contributes to

  2003cites this paper
• Increased E‐selectin, IL‐8 and IL‐10 gene expression in human skin after minimal trauma

  2003influential citation
• Antigen presentation by keratinocytes directs autoimmune skin disease

  2003cites this paper
• By IL-1 Signaling, Monocyte-Derived Cells Dramatically Enhance the Epidermal Antimicrobial Response to Lipopolysaccharide1

  2003cites this paper
• Neutrophil CD11b, L‐selectin and Fc IgA receptors in patients with dermatitis herpetiformis

  2002cites this paper
• Dry eye and delayed tear clearance: "a call to arms.".

  2002cites this paper
• Induction of apoptosis in vascular smooth muscle cells by mechanical stretch.

  2002cites this paper