Attenuated Activation of Homeostatic Glucocorticoid in Keratinocytes Induces Alloknesis via Aberrant Artemin Production

作者:Matsumoto Akira*; Murota Hiroyuki; Terao Mika; Katayama Ichiro
来源:Journal of Investigative Dermatology, 2018, 138(7): 1491-1500.
DOI:10.1016/j.jid.2018.02.010

摘要

Intense chronic itch significantly reduces quality of life for atopic dermatitis patients, impairing daily activity. Although abnormal itch sensation can be induced by innocuous stimuli, known as alloknesis, the mechanisms driving this process remain obscure. Psychological and environmental stimuli are known to aggravate atopic dermatitis symptoms. Recently, the enzyme 11 beta-hydroxysteroid dehydrogenase-1 (HSD11 beta 1), which is expressed in keratinocytes, has been implicated in maintaining homeostasis against environmental stimuli by activating endogenous glucocorticoids. To investigate the role of HSD11 beta 1 in keratinocytes, we generated keratinocyte-specific Hsd11b1-knockout (Hsd11b1(KC-/-)) mice and analyzed skin phenotype. Hsd11b1(KC-/-)mice exhibited abnormal cutaneous innervation and skin sensitivity, including light mechanical stimulus-evoked itch (i.e., alloknesis). Attenuated endogenous glucocorticoid activation induced by aberrant artemin production in keratinocytes was involved in alloknesis in Hsd11b1(KC-/-) mice. Finally, we observed a significant negative correlation between expression of HSD11 beta 1 and artemin in human skin with and without AD. These results suggest that endogenous glucocorticoids that maintain skin homeostasis in the epidermis affect both skin innervation and cutaneous sensation. Modulation of HSD11 beta 1 activation could be a therapeutic target for sensitive or itchy skin.

  • 出版日期2018-7