Cetirizine and hydrocortisone differentially regulate ICAM-1 expression and chemokine release in cultured human keratinocytes

C. Albanesi, S. Pastore, E. Fanales-Belasio, G. Girolomoni

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background: Cetirizine is a Hi histamine antagonist which possesses anti-inflammatory properties through inhibition of leucocyte recruitment and activation, and reduction of ICAM-1 expression on mucosal epithelial cells. No studies have addressed the potential anti-inflammatory activities of cetirizine on skin keratinocytes. Objectives: Cetirizine and hydrocortisone were compared in their capacity to counteract human keratinocytes activation by IFNγ. In particular, expression of immuno-modulatory membrane molecules and chemokine release have been examined. Methods: Keratinocyte cultures established from normal skin of healthy donors were activated by IFNγ (100- 500 U/mL) in the absence or presence of cetirizine (10-3 - 103 μM) or hydrocortisone (10-3 -102 μM), and tested for expression of ICAM-1, HLA- DR, MHC class I and CD40 as well as for release of RANTES, IL-8, macrophage chemotactic protein-1 (MCP-1) and granulocyte macrophage-colony stimulating factor (GM-CSF). Results: Cetirizine at high concentrations (102-103 μM) markedly inhibited IFNγ-induced expression of membrane ICAM-1, HLA-DR and up-regulation of MHC class I, but had no effect on CD40 expression. In contrast, hydrocortisone (102 μM) enhanced IFNγ-induced membrane ICAM-1, reduced expression of HLA-DR and did not alter expression of MHC class I and CD40. Consistently, high doses of cetirizine decreased, whereas hydrocortisone increased, soluble ICAM-1 levels in the supernatants of IFN- γ-treated keratinocytes. The inhibiting and stimulating effects of cetirizine and hydrocortisone, respectively, on ICAM-1 expression were confirmed at the mRNA level by Northern blot analysis. Finally, cetirizine, but not hydrocortisone, inhibited the release of MCP-1 and RANTES from IFNγ- stimulated keratinocytes. In contrast, hydrocortisone, but not cetirizine, reduced GM-CSF and IL-8 release. Conclusions: The results indicate that cetirizine has the capacity to block the IFNγ-induced activation of keratinocytes, and thus can exert important regulatory effects on TH1 cell- mediated immune responses in the skin. The high doses required for evidencing these activities suggest the potential benefits of a topical use of cetirizine.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalClinical and Experimental Allergy
Volume28
Issue number1
DOIs
Publication statusPublished - 1998

Fingerprint

Cetirizine
Intercellular Adhesion Molecule-1
Keratinocytes
Chemokines
Hydrocortisone
HLA-DR Antigens
Chemokine CCL5
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-8
Skin
Membranes
Anti-Inflammatory Agents
Macrophages
Histamine Antagonists
Northern Blotting
Proteins
Leukocytes
Up-Regulation

Keywords

  • Adhesion molecules
  • Cetirizine
  • Chemokines
  • Hydrocortisone
  • Skin immune responses

ASJC Scopus subject areas

  • Immunology

Cite this

Cetirizine and hydrocortisone differentially regulate ICAM-1 expression and chemokine release in cultured human keratinocytes. / Albanesi, C.; Pastore, S.; Fanales-Belasio, E.; Girolomoni, G.

In: Clinical and Experimental Allergy, Vol. 28, No. 1, 1998, p. 101-109.

Research output: Contribution to journalArticle

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abstract = "Background: Cetirizine is a Hi histamine antagonist which possesses anti-inflammatory properties through inhibition of leucocyte recruitment and activation, and reduction of ICAM-1 expression on mucosal epithelial cells. No studies have addressed the potential anti-inflammatory activities of cetirizine on skin keratinocytes. Objectives: Cetirizine and hydrocortisone were compared in their capacity to counteract human keratinocytes activation by IFNγ. In particular, expression of immuno-modulatory membrane molecules and chemokine release have been examined. Methods: Keratinocyte cultures established from normal skin of healthy donors were activated by IFNγ (100- 500 U/mL) in the absence or presence of cetirizine (10-3 - 103 μM) or hydrocortisone (10-3 -102 μM), and tested for expression of ICAM-1, HLA- DR, MHC class I and CD40 as well as for release of RANTES, IL-8, macrophage chemotactic protein-1 (MCP-1) and granulocyte macrophage-colony stimulating factor (GM-CSF). Results: Cetirizine at high concentrations (102-103 μM) markedly inhibited IFNγ-induced expression of membrane ICAM-1, HLA-DR and up-regulation of MHC class I, but had no effect on CD40 expression. In contrast, hydrocortisone (102 μM) enhanced IFNγ-induced membrane ICAM-1, reduced expression of HLA-DR and did not alter expression of MHC class I and CD40. Consistently, high doses of cetirizine decreased, whereas hydrocortisone increased, soluble ICAM-1 levels in the supernatants of IFN- γ-treated keratinocytes. The inhibiting and stimulating effects of cetirizine and hydrocortisone, respectively, on ICAM-1 expression were confirmed at the mRNA level by Northern blot analysis. Finally, cetirizine, but not hydrocortisone, inhibited the release of MCP-1 and RANTES from IFNγ- stimulated keratinocytes. In contrast, hydrocortisone, but not cetirizine, reduced GM-CSF and IL-8 release. Conclusions: The results indicate that cetirizine has the capacity to block the IFNγ-induced activation of keratinocytes, and thus can exert important regulatory effects on TH1 cell- mediated immune responses in the skin. The high doses required for evidencing these activities suggest the potential benefits of a topical use of cetirizine.",
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T1 - Cetirizine and hydrocortisone differentially regulate ICAM-1 expression and chemokine release in cultured human keratinocytes

AU - Albanesi, C.

AU - Pastore, S.

AU - Fanales-Belasio, E.

AU - Girolomoni, G.

PY - 1998

Y1 - 1998

N2 - Background: Cetirizine is a Hi histamine antagonist which possesses anti-inflammatory properties through inhibition of leucocyte recruitment and activation, and reduction of ICAM-1 expression on mucosal epithelial cells. No studies have addressed the potential anti-inflammatory activities of cetirizine on skin keratinocytes. Objectives: Cetirizine and hydrocortisone were compared in their capacity to counteract human keratinocytes activation by IFNγ. In particular, expression of immuno-modulatory membrane molecules and chemokine release have been examined. Methods: Keratinocyte cultures established from normal skin of healthy donors were activated by IFNγ (100- 500 U/mL) in the absence or presence of cetirizine (10-3 - 103 μM) or hydrocortisone (10-3 -102 μM), and tested for expression of ICAM-1, HLA- DR, MHC class I and CD40 as well as for release of RANTES, IL-8, macrophage chemotactic protein-1 (MCP-1) and granulocyte macrophage-colony stimulating factor (GM-CSF). Results: Cetirizine at high concentrations (102-103 μM) markedly inhibited IFNγ-induced expression of membrane ICAM-1, HLA-DR and up-regulation of MHC class I, but had no effect on CD40 expression. In contrast, hydrocortisone (102 μM) enhanced IFNγ-induced membrane ICAM-1, reduced expression of HLA-DR and did not alter expression of MHC class I and CD40. Consistently, high doses of cetirizine decreased, whereas hydrocortisone increased, soluble ICAM-1 levels in the supernatants of IFN- γ-treated keratinocytes. The inhibiting and stimulating effects of cetirizine and hydrocortisone, respectively, on ICAM-1 expression were confirmed at the mRNA level by Northern blot analysis. Finally, cetirizine, but not hydrocortisone, inhibited the release of MCP-1 and RANTES from IFNγ- stimulated keratinocytes. In contrast, hydrocortisone, but not cetirizine, reduced GM-CSF and IL-8 release. Conclusions: The results indicate that cetirizine has the capacity to block the IFNγ-induced activation of keratinocytes, and thus can exert important regulatory effects on TH1 cell- mediated immune responses in the skin. The high doses required for evidencing these activities suggest the potential benefits of a topical use of cetirizine.

AB - Background: Cetirizine is a Hi histamine antagonist which possesses anti-inflammatory properties through inhibition of leucocyte recruitment and activation, and reduction of ICAM-1 expression on mucosal epithelial cells. No studies have addressed the potential anti-inflammatory activities of cetirizine on skin keratinocytes. Objectives: Cetirizine and hydrocortisone were compared in their capacity to counteract human keratinocytes activation by IFNγ. In particular, expression of immuno-modulatory membrane molecules and chemokine release have been examined. Methods: Keratinocyte cultures established from normal skin of healthy donors were activated by IFNγ (100- 500 U/mL) in the absence or presence of cetirizine (10-3 - 103 μM) or hydrocortisone (10-3 -102 μM), and tested for expression of ICAM-1, HLA- DR, MHC class I and CD40 as well as for release of RANTES, IL-8, macrophage chemotactic protein-1 (MCP-1) and granulocyte macrophage-colony stimulating factor (GM-CSF). Results: Cetirizine at high concentrations (102-103 μM) markedly inhibited IFNγ-induced expression of membrane ICAM-1, HLA-DR and up-regulation of MHC class I, but had no effect on CD40 expression. In contrast, hydrocortisone (102 μM) enhanced IFNγ-induced membrane ICAM-1, reduced expression of HLA-DR and did not alter expression of MHC class I and CD40. Consistently, high doses of cetirizine decreased, whereas hydrocortisone increased, soluble ICAM-1 levels in the supernatants of IFN- γ-treated keratinocytes. The inhibiting and stimulating effects of cetirizine and hydrocortisone, respectively, on ICAM-1 expression were confirmed at the mRNA level by Northern blot analysis. Finally, cetirizine, but not hydrocortisone, inhibited the release of MCP-1 and RANTES from IFNγ- stimulated keratinocytes. In contrast, hydrocortisone, but not cetirizine, reduced GM-CSF and IL-8 release. Conclusions: The results indicate that cetirizine has the capacity to block the IFNγ-induced activation of keratinocytes, and thus can exert important regulatory effects on TH1 cell- mediated immune responses in the skin. The high doses required for evidencing these activities suggest the potential benefits of a topical use of cetirizine.

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