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Atopic dermatitis (AD) is attributable to both a genetic predisposition and environmental factors. Among numerous cytokines involved in the pathogenesis of AD, interleukin‐33 (IL‐33), reportedly escaping exocytotically in response to a scratch, is abundantly expressed in the skin tissues of patients with AD and is postulated to induce inflammatory and autoimmune responses. In this study, we first demonstrated that peptidylprolyl cis/trans isomerase, NIMA‐interacting 1 (Pin1), a unique enzyme which isomerizes the proline residues of target proteins, is abundantly expressed in keratinocytes, and that the areas where it is present in the skin tissues of AD patients became expanded due to hyperkeratosis. Thus, we investigated the effects of Pin1 on the regulation of IL‐33 expression using the human keratinocyte cell line HaCaT. Interestingly, silencing of the Pin1 gene or treatment with Pin1 inhibitors dramatically reduced IL‐33 expressions in HaCaT cells, although Pin1 overexpression did not elevate it. Subsequently, we showed that Pin1 binds to STAT1 and the nuclear factor‐kappaB (NF‐κB) subunit p65. Silencing the Pin1 gene with small interfering RNAs significantly reduced the phosphorylation of p65, while no marked effects of Pin1 on the STAT1 pathway were detected. Thus, it is likely that Pin1 contributes to increased expression of IL‐33 via the NF‐κB subunit p65 in HaCaT cells, at least modestly. Nevertheless, further study is necessary to demonstrate the pathogenic roles of Pin1 and IL‐33 in AD development.

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Background Prostate cancer (PCa) is a major cause of cancer morbidity and mortality for men globally, and androgen signaling clearly drives its onset and progression. Androgen receptor (AR) regulation is complex and remains elusive, despite several studies tackling these issues. Therefore, elucidating the mechanism(s) underlying AR regulation is a potentially promising approach to suppressing PCa. Methods We report that Par14, one isoform of the prolyl isomerases homologous to Pin1, is a critical regulator of AR transcriptional activity and is essential for PCa cell growth. Results Par14 was shown to be overexpressed in PCa, based on analyses of deposited data. Importantly, overexpression of Par14 significantly enhanced androgen‐sensitive LNCap cell growth. In contrast, silencing of Par14 dramatically decreased cell growth in LNCap cells by causing cell cycle arrest. Mechanistically, silencing of the Par14 gene dramatically induced cyclin‐dependent kinase inhibitor p21 at both the mRNA and the protein level through modulating the localization of p53. In addition, suppression of Par14 in LNCap cells was shown to downregulate the expressions of androgen response genes, at both the mRNA and the protein level, induced by dihydrotestosterone. Par14 was shown to directly associate with AR in nuclei via its DNA‐binding domain and augment AR transcriptional activity. Conclusion Thus, Par14 plays a critical role in PCa progression, and its enhancing effects on AR signaling are likely to be involved in the underlying molecular mechanisms. These findings suggest Par14 to be a promising therapeutic target for PCa.