title: Interleukin-15 inhibits the expression of differentiation markers induced by Ca(2+) in keratinocytes.
abstract: Interleukin (IL)-15 is an important proinflammatory cytokine that can protect epidermal keratinocytes (KCs) from ultraviolet-induced apoptosis and plays a role in the pathogenesis of psoriasis. However, the impact of IL-15 on KC differentiation remains unknown. In this study, isolated human primary epidermal KCs were treated with various concentrations of IL-15 for different times, and the expression of differentiation markers (keratin 1, involucrin and loricrin) and p53 as well as the activation of ERK, AKT and Notch induced by IL-15 in the absence or presence of Ca(2+) was detected by real-time PCR and Western blot. The results showed that stimulation with Ca(2+) alone increased the expression of KC differentiation markers and p53 and promoted the activation of Notch1. Pretreatment with IL-15 resulted in a decrease in the Ca(2+) -induced expression of KC differentiation markers and p53. Additionally, Ca(2+) continually inhibited the phosphorylation of ERK1/2 and activated AKT, and IL-15 reduced the effect of Ca(2+) on ERK1/2 and AKT. FR180204, a specific inhibitor of ERK1/2 phosphorylation, slightly attenuated the effect of Ca(2+) on the expression of differentiation markers and p53 and the activation of Notch1. In contrast, MK-2206, an inhibitor of pAKT, strongly blocked the expression of the differentiation markers and p53 and the activation of Notch1. An anti-IL-15 antibody neutralized the effect of IL-15 on KC differentiation. These results indicate that IL-15 inhibits the Ca(2+) -induced differentiation of KCs, mainly via the attenuation of Ca(2+) -stimulated PI3K-AKT signalling.
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Luan
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Feng-Wei
authors.initials: FW
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Dermatology at the 1st Hospital, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Liang-Dan
authors.initials: LD
authors.lastname: Sun
authors.affiliation: Institute of Dermatology at the 1st Hospital, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.|Institute of Dermatology at the 1st Hospital, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Sheng-Quan
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Institute of Dermatology at the 1st Hospital, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation; D015870:Gene Expression; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism
chemical_list: C569274:IL15 protein, human; D019409:Interleukin-15; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium
keywords: IL-15; differentiation; keratinocytes; signalling pathway