PT  - JOURNAL ARTICLE
AU  - Lee, R T
AU  - Briggs, W H
AU  - Cheng, G C
AU  - Rossiter, H B
AU  - Libby, P
AU  - Kupper, T
TI  - Mechanical deformation promotes secretion of IL-1 alpha and IL-1 receptor antagonist.
DP  - 1997 Nov 15
TA  - The Journal of Immunology
PG  - 5084--5088
VI  - 159
IP  - 10
4099  - http://www.jimmunol.org/content/159/10/5084.short
4100  - http://www.jimmunol.org/content/159/10/5084.full
SO  - J. Immunol.1997 Nov 15; 159
AB  - 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.