Secukinumab promotes engagement of cholecystokinin and its receptor in epidermal keratinocytes of psoriasis patients

Abstract

Psoriasis is mediated by immune cells and epidermal keratinocytes. Interleukin (IL)-17A is one of the most critical cytokines involved in the pathogenesis of psoriasis, as it stimulates keratinocytes to produce various cytokines and chemokines that recruit inflammatory cells to the skin. 1 Therefore, neutralizing biologics against IL-17A, as exemplified by secuk

Cholecystokinin Receptor Antagonist Suppresses Melanoma Growth by Inducing Apoptosis of Tumor Cells

“…The specificity of the antibodies was also confirmed by staining normal human skin cells with anti-CCKAR, anti-CCK, or rabbit IgG isotype control antibodies ( Figure 2 ). Similar to our previous studies ( Funakoshi et al., 2020 , 2019 ), epidermal KCs were positively stained with anti-CCKAR and anti-CCK antibodies but not with rabbit IgG isotype control antibody.

Figure 1 CCKAR is expressed in melanoma cells.

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“…Next, we evaluated the expression levels of CCK and its receptors in several skin tumor cell lines. We used normal human epidermal keratinocytes (NHEK) and Jurkat cells as positive controls for CCKAR and CCKBR, respectively (Funakoshi et al, 2020, Funakoshi et al, 2019, Lignon et al, 1991. Flow cytometric analysis revealed that B16-F1 mouse melanoma and A375 human melanoma cells expressed CCKAR, while CCKBR was hardly detected in these cells (Figure 3a).…”

“…CCK plays an anti-inflammatory role by suppressing cytokine production from epidermal KCs through CCKAR ( Funakoshi et al., 2019 ). IL-17A decreases the expression levels of both CCK and CCKAR in KCs ( Funakoshi et al., 2020 , 2019 ). We also showed that CCK suppresses substance P‒induced itch by suppressing mast cell degranulation ( Fukamachi et al., 2011 ).…”