Zinc finger protein A20 is involved in the antipsoriatic effect of calcipotriol

Abstract

Calcipotriol exhibits its antipsoriatic function through suppressing A20 expression and stabilizing negative regulators of the NF-κB pathway.

The evolving regulatory role of ubiquitin-editing enzyme A20 in psoriasis during calcipotriol treatment

“…6 In this issue of the BJD, Liu et al found that the ubiquitinediting enzyme A20 and NF-jB p65 were strongly expressed in lesional psoriatic skin compared with nonlesional skin. 7 The authors observe that treatment with calcipotriol decreased A20 and NF-jB p65 in lesional psoriatic skin, consistent with the decrease of A20 in the skin of calcipotriol-treated K14-vascular endothelial growth factor (VEGF) mice, a murine psoriasis-like model. To further elucidate the role of A20 in psoriasis, the authors stimulated keratinocytes with a cocktail of pro-inflammatory cytokines and observed that calcipotriol increased A20 expression within 24 h and subsequently decreased the A20 expression as well as NF-jB p65.…”

“…In this issue of the BJD , Liu et al . found that the ubiquitin‐editing enzyme A20 and NF‐κB p65 were strongly expressed in lesional psoriatic skin compared with nonlesional skin . The authors observe that treatment with calcipotriol decreased A20 and NF‐κB p65 in lesional psoriatic skin, consistent with the decrease of A20 in the skin of calcipotriol‐treated K14‐vascular endothelial growth factor (VEGF) mice, a murine psoriasis‐like model.…”

“…On the other, toxicology experiments in animals (cynomolgus monkey) reached maximum serum concentrations of IPH4102 > 2000 lg mL À1 for several days without any toxicity. 7 A phase I clinical trial to treat patients with advanced/relapsed cutaneous T-cell lymphoma with IPH4102 is being conducted.…”

“…The effects of vitamin D and its analogues on keratinocytes under pathological conditions reveal several layers of complexity. To date, A20 has been suggested to inhibit proliferation and apoptosis, which is inconsistent with the pathology of psoriasis and the strong expression of A20 found in lesional psoriatic skin by Liu et al . A20 has also been posited to inhibit the NF‐κB pathway; however, a strong expression of NF‐κB is observed in psoriasis, suggesting that A20 is disabled, dysfunctional in patients with psoriasis or that the potent pro‐inflammatory signals can drive NF‐κB activation despite high levels of A20.…”

Modulation of allergic inflammation in the lung by a peptide derived from Mycobacteria tuberculosis chaperonin 60.1

“…The role of A20 in inflammatory conditions has been well documented. An important anti‐inflammatory role for this ubiquitin has been reported in arthritis, auto‐immune diseases, cardiovascular diseases, cystic fibrosis, chronic obstructive pulmonary disease (COPD), allergies and asthma . In addition, the modulation of the expression of A20 has been demonstrated to be an important mechanism of action of certain drugs including methotrexate, quercetin and the combination of long‐acting β 2 ‐adrenoceptor agonistsand glucocorticoids .…”