Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1 alpha) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1).
Pro-inflammatory cytokines mediate their biological functions after they are secreted or released from intracellular to extracellular milieu. Keratinocytes have proven to be able to produce various cytokines including IL-1 and IL-8. Dysregulations of IL-1 and IL-8 were found in psoriatic lesions. Recently, vitamin D3 (VD3) was found to be an effective and safe therapy for psoriasis. In the present study, we investigated the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogue MC903 on IL-1 alpha and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1 alpha but secreted less. In contrast, they produced less IL-8 and almost all molecules were secreted to the culture supernatants. Treatment of unstimulated NHKs with 1,25(OH)2D3 or MC903 showed little effects on IL-1 alpha production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNF alpha), both IL-1 alpha and IL-8 secretions were enhanced and these enhancements were inhibited by 1,25(OH)2D3 or MC903. Stimulation of NHKs with phorbol 12-myristate 13-acetate(PMA) and lipopolysaccharide(LPS) resulted in an increase of IL-8 and decrease of IL-1 alpha in the culture supernatants. Addition of 1,25(OH)2D3 or MC903 inhibited the increased secretion of IL-8 but restored decreased secretion of IL-1 alpha from stimulated NHKs dose dependently. Hydrocortisone and cyclosporin A showed similar inhibitory effects on PMA/LPS-increased IL-8 secretion from NHKs but had little effect of restoring IL-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
J Z
JZ
Department of Dermatology, Fukushima Medical College, Japan.
Maruyama
K
K
Ono
I
I
Iwatsuki
K
K
Kaneko
F
F
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002762:Cholecalciferol / Q000031:analogs & derivatives*; D003879:Dermatologic Agents / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003879:Dermatologic Agents; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C055085:calcipotriene; D002762:Cholecalciferol; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate