Protein kinase CK2 is a constitutively active and ubiquitously expressed serine/threonine
kinase that is closely associated with various types of cancers, autoimmune disorders,
and inflammation. However, the role of CK2 in psoriasis remains unknown. Herein, the
study indicated elevated expression of CK2 in skin lesions from patients with psoriasis
and from psoriasis-like mice. In the psoriasis-like mouse model, the CK2-specific
inhibitor CX-4945 ameliorated imiquimod-induced psoriasis symptoms with reduced proliferation,
abnormal differentiation, inflammatory cytokine production (especially IL-17A) of
keratinocytes, and infiltration of γδ T cells. In in vitro studies, exogenous CK2 promoted hyperproliferation and abnormal differentiation of
human keratinocytes, which were reversed by the suppression of CK2 with CX-4945 or
siRNA. Furthermore, knockdown of CK2 reduced IL-17A expression and abolished IL-17A–induced
proliferation and inflammatory cytokine expression in keratinocytes. Interestingly,
IL-17A increased the expression of CK2 in keratinocytes, thereby establishing a positive
feedback loop. In addition, suppression of CK2 inhibited the activation of STAT3 and
Akt signaling pathways in human keratinocytes and imiquimod-induced psoriatic lesions
of mice. These findings indicate that a highly expressed CK2 level in the skin lesions
is required in the development of psoriasis by promoting epidermal hyperplasia, abnormal
differentiation, and inflammatory response via regulation of the STAT3 and Akt signaling
pathways. CK2 may be a target for the treatment of psoriasis.
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Article info
Publication history
Accepted:
January 26,
2023
Footnotes
Supported by National Natural Science Foundation of China (grant no. 81972942), the Chongqing Science and Health Joint Medical Research Project (grant no. 2020FYYX017), the Chongqing Innovative Support Program for Returned Overseas Chinese Scholars (grant no. cx2020103), and the High-level Medical Reserved Personnel Training Project of Chongqing.
Disclosures: None declared.
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© 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
