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Published on: September 27, 2017
Effects of indomethacin and dexamethasone on mechanical scratching-induced cutaneous barrier disruption in mice
Yusuke Honma1, Iwao Arai, Takanobu Sakurai
1Department of Pharmacology Laboratory, Medical Research Laboratories, Taisho Pharmaceutical Co. Ltd, Saitama, Japan. y.honma@po.rd.taisho.co.jp
Abstract:
Effects of indomethacin and dexamethasone on recovery of cutaneous barrier disruption induced by mechanical scratching were examined. Cutaneous barrier was disrupted by scratching using a stainless-steel wire brush (mechanical scratching) and compared to cutaneous application of acetone/ether (1:1) mixture (AE) and tape-stripping. Increase of transepidermal water loss (TEWL), as an indicator of a broken skin barrier, and recovery period for mechanical scratching were higher and longer than those for AE treatment and tape-stripping and we also confirmed the severity of skin damage in a histological study. Topical application of moisturizers showed a temporal effect, rapidly decreased TEWL on mechanical scratching- or AE treatment-induced cutaneous barrier disruption, and gradually increased base levels from 4 to 12 h after treatment. Topical application of indomethacin or dexamethasone prolonged the recovery period for the cutaneous barrier, and concomitant use further worsened the status of the barrier. Additionally, we examined the effects of prostaglandins (PGs) and inflammatory cytokine on mechanical scratching-induced cutaneous barrier disruption pretreated with indomethacin and dexamethasone. As a results, PGD2 and interleukin (IL)-1beta significantly accelerated the recovery of cutaneous barrier disruption by mechanical scratching but such was not the case with PGE2, IL-1alpha, and tumor necrosis factor-alpha treatment. These results suggest that indomethacin and dexamethasone prolonged the recovery period caused by inhibition of PGD2 and IL-1beta. Mechanical scratching-induced cutaneous barrier disruption may be a useful method for evaluating means of recovery from skin damage.
Insights
Mechanical scratching severely disrupts the skin barrier. Indomethacin and dexamethasone delay healing by inhibiting beneficial prostaglandins (PGs) and interleukin-1 beta (IL-1beta).
Area of Science:
- Dermatology
- Wound Healing
- Skin Barrier Function
Background:
- Mechanical scratching is a common cause of skin barrier disruption.
- Understanding factors influencing skin barrier recovery is crucial for dermatological treatments.
Purpose of the Study:
- To investigate the impact of indomethacin and dexamethasone on skin barrier recovery after mechanical scratching.
- To evaluate the role of prostaglandins and inflammatory cytokines in modulating this recovery process.
Main Methods:
- Mechanical scratching was used to induce cutaneous barrier disruption.
- Transepidermal water loss (TEWL) was measured to assess barrier integrity.
- Histological studies evaluated skin damage severity.
- The effects of indomethacin, dexamethasone, prostaglandins (PGs), and cytokines were examined.
Main Results:
- Mechanical scratching induced more significant and prolonged barrier disruption compared to acetone/ether or tape-stripping.
- Indomethacin and dexamethasone application extended the skin barrier recovery period.
- Prostaglandin D2 (PGD2) and Interleukin-1 beta (IL-1beta) significantly accelerated barrier recovery.
- PGE2, IL-1alpha, and TNF-alpha did not show a significant effect on recovery.
Conclusions:
- Indomethacin and dexamethasone impair skin barrier recovery, likely by inhibiting PGD2 and IL-1beta.
- Mechanical scratching serves as a valuable model for studying skin barrier repair mechanisms.
- Targeting PGD2 and IL-1beta pathways may offer therapeutic potential for enhancing skin barrier function.
