Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1α) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1)

Jian Zhong Zhang, Kohji Maruyama, Ichiro Ono, Keiji Iwatsuki, Fumio Kaneko

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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-1α and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1α 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-1α production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNFα), both IL-1α 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-1α 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-1α 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 on restoring IL-1α. Cells of HSC-1, a human squamous cell carcinoma cell line, constitutively produced and secreted both IL-1α and IL-8. 1,25(OH)2D3 and MC903 inhibited the production of both cytokines. These results suggest that VD3 is effective in terms of regulation of both IL-1α and IL-8 secretion by keratinocytes, which may contribute to its clinical efficacy for psoriasis.

Original languageEnglish
Pages (from-to)24-31
Number of pages8
JournalJournal of Dermatological Science
Volume7
Issue number1
DOIs
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Interleukin-1alpha
Calcitriol
Cholecalciferol
Interleukin-8
Keratinocytes
Squamous Cell Carcinoma
Cells
Cell Line
Cytokines
Psoriasis
Lipopolysaccharides
Acetates
Epithelial Cells
Cyclosporine
Hydrocortisone
Tumor Necrosis Factor-alpha

Keywords

  • cell culture
  • Interleukin-1 alpha
  • Interleukin-8
  • Keratinocytes
  • Vitamin D

ASJC Scopus subject areas

  • Dermatology

Cite this

Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1α) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1). / Zhang, Jian Zhong; Maruyama, Kohji; Ono, Ichiro; Iwatsuki, Keiji; Kaneko, Fumio.

In: Journal of Dermatological Science, Vol. 7, No. 1, 1994, p. 24-31.

Research output: Contribution to journalArticle

@article{20c6b2078a424ddfa788723c685aa1d0,
title = "Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1α) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1)",
abstract = "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-1α and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1α 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-1α production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNFα), both IL-1α 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-1α 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-1α 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 on restoring IL-1α. Cells of HSC-1, a human squamous cell carcinoma cell line, constitutively produced and secreted both IL-1α and IL-8. 1,25(OH)2D3 and MC903 inhibited the production of both cytokines. These results suggest that VD3 is effective in terms of regulation of both IL-1α and IL-8 secretion by keratinocytes, which may contribute to its clinical efficacy for psoriasis.",
keywords = "cell culture, Interleukin-1 alpha, Interleukin-8, Keratinocytes, Vitamin D",
author = "Zhang, {Jian Zhong} and Kohji Maruyama and Ichiro Ono and Keiji Iwatsuki and Fumio Kaneko",
year = "1994",
doi = "10.1016/0923-1811(94)90018-3",
language = "English",
volume = "7",
pages = "24--31",
journal = "Journal of Dermatological Science",
issn = "0923-1811",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1α) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1)

AU - Zhang, Jian Zhong

AU - Maruyama, Kohji

AU - Ono, Ichiro

AU - Iwatsuki, Keiji

AU - Kaneko, Fumio

PY - 1994

Y1 - 1994

N2 - 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-1α and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1α 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-1α production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNFα), both IL-1α 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-1α 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-1α 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 on restoring IL-1α. Cells of HSC-1, a human squamous cell carcinoma cell line, constitutively produced and secreted both IL-1α and IL-8. 1,25(OH)2D3 and MC903 inhibited the production of both cytokines. These results suggest that VD3 is effective in terms of regulation of both IL-1α and IL-8 secretion by keratinocytes, which may contribute to its clinical efficacy for psoriasis.

AB - 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-1α and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1α 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-1α production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNFα), both IL-1α 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-1α 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-1α 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 on restoring IL-1α. Cells of HSC-1, a human squamous cell carcinoma cell line, constitutively produced and secreted both IL-1α and IL-8. 1,25(OH)2D3 and MC903 inhibited the production of both cytokines. These results suggest that VD3 is effective in terms of regulation of both IL-1α and IL-8 secretion by keratinocytes, which may contribute to its clinical efficacy for psoriasis.

KW - cell culture

KW - Interleukin-1 alpha

KW - Interleukin-8

KW - Keratinocytes

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=0028346980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028346980&partnerID=8YFLogxK

U2 - 10.1016/0923-1811(94)90018-3

DO - 10.1016/0923-1811(94)90018-3

M3 - Article

C2 - 8193081

AN - SCOPUS:0028346980

VL - 7

SP - 24

EP - 31

JO - Journal of Dermatological Science

JF - Journal of Dermatological Science

SN - 0923-1811

IS - 1

ER -