Prokineticin 2 Plays a Pivotal Role in Psoriasis

Psoriasis is histologically characterized by keratinocytes (KC) hyperproliferation, inflammation, and increased angiogenesis, but the pathological factor responsible for these symptoms is unknown. Here, a neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and mouse psoriatic skins but no significant change in other autoimmune diseases, suggesting that PK2 is a psoriasis-specific factor. Bacterial products significantly up-regulated PK2, implying that infection induces PK2 over-expression. PK2 promoted KC and macrophage to produce interleukin-1 (IL-1), the central player of inflammation and psoriasis, which acts on adjacent fibroblast to induce inflammatory cascades and KC hyperproliferation. IL-1 feeds back on macrophages to induce PK2 production to perpetuate PK2-IL-1 positive feedback loop. PK2 also promoted angiogenesis, another psoriatic symptom. In mouse models, PK2 over-expression aggravated psoriasis while its knock-down inhibited pathological development. The results indicate that PK2 over-production perpetuates psoriatic symptoms by creating PK-2-IL-1 vicious loop. PK2 is a central player in psoriasis and a promising psoriasis-specific target.
Highlights • High level of PK2 is found in psoriasis but not in other autoimmunity diseases. • Bacterial products induce PK2 over-expression to promote IL-1 signal. • IL-1 induces PK2 secretion to create a PK2-IL-1 circle to perpetuate symptoms. • PK2 is a central player in psoriasis and may be a psoriasis-specific target. Psoriasis is a common autoimmune disease whose pathogenesis remains poorly understood. We found that PK2 was highly expressed in psoriasis but not in other autoimmune diseases. To investigate the role of PK2 in psoriasis, the effect of PK2 on keratinocyte proliferation, inflammation and angiogenesis were analyzed. PK2 expression mediated by virus in psoriasis was applied. The results demonstrated that PK2 promoted psoriasis development. PK2 over-expression in mouse model aggravates psoriasis while knock-down of PK2 improves the disease. PK2 plays a pivotal role in psoriasis.