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

R T Lee, W H Briggs, G C Cheng, H B Rossiter, P Libby and T Kupper
J Immunol November 15, 1997, 159 (10) 5084-5088;
R T Lee
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W H Briggs
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G C Cheng
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H B Rossiter
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P Libby
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T Kupper
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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.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 159, Issue 10
15 Nov 1997
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Mechanical deformation promotes secretion of IL-1 alpha and IL-1 receptor antagonist.
R T Lee, W H Briggs, G C Cheng, H B Rossiter, P Libby, T Kupper
The Journal of Immunology November 15, 1997, 159 (10) 5084-5088;

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Mechanical deformation promotes secretion of IL-1 alpha and IL-1 receptor antagonist.
R T Lee, W H Briggs, G C Cheng, H B Rossiter, P Libby, T Kupper
The Journal of Immunology November 15, 1997, 159 (10) 5084-5088;
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