PMID- 9537772
OWN - NLM
STAT- MEDLINE
DCOM- 19980403
LR  - 20190831
IS  - 0954-7894 (Print)
IS  - 0954-7894 (Linking)
VI  - 28
IP  - 1
DP  - 1998 Jan
TI  - Cetirizine and hydrocortisone differentially regulate ICAM-1 expression and 
      chemokine release in cultured human keratinocytes.
PG  - 101-9
AB  - BACKGROUND: Cetirizine is a H1 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 IFNgamma. 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 IFNgamma (100-500 U/mL) in the 
      absence or presence of cetirizine (10(-3)-10(3) microM) or hydrocortisone 
      (10(-3)-10(2) microM), 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 (10(2)-10(3) microM) markedly inhibited 
      IFNgamma-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 (10(2) 
      microM) enhanced IFNgamma-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 IFNgamma-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 IFNgamma-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 IFNgamma-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.
FAU - Albanesi, C
AU  - Albanesi C
AD  - Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, 
      Italy.
FAU - Pastore, S
AU  - Pastore S
FAU - Fanales-Belasio, E
AU  - Fanales-Belasio E
FAU - Girolomoni, G
AU  - Girolomoni G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histamine H1 Antagonists)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - WI4X0X7BPJ (Hydrocortisone)
RN  - YO7261ME24 (Cetirizine)
SB  - IM
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antineoplastic Agents/administration & dosage/pharmacology
MH  - CD40 Antigens/drug effects/genetics
MH  - Cells, Cultured
MH  - Cetirizine/*pharmacology
MH  - Chemokine CCL2/antagonists & inhibitors/metabolism
MH  - Chemokine CCL5/antagonists & inhibitors/metabolism
MH  - Chemokines/*metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & 
      inhibitors/metabolism
MH  - HLA-DR Antigens/biosynthesis/drug effects
MH  - Histamine H1 Antagonists/*pharmacology
MH  - Humans
MH  - Hydrocortisone/*pharmacology
MH  - Intercellular Adhesion Molecule-1/*biosynthesis/*drug effects
MH  - Interferon-gamma/administration & dosage/pharmacology
MH  - Interleukin-8/antagonists & inhibitors/metabolism
MH  - Keratinocytes/*cytology/drug effects/metabolism
MH  - RNA, Messenger/analysis/genetics
EDAT- 1998/04/16 00:00
MHDA- 1998/04/16 00:01
CRDT- 1998/04/16 00:00
PHST- 1998/04/16 00:00 [pubmed]
PHST- 1998/04/16 00:01 [medline]
PHST- 1998/04/16 00:00 [entrez]
AID - 10.1046/j.1365-2222.1998.00206.x [doi]
PST - ppublish
SO  - Clin Exp Allergy. 1998 Jan;28(1):101-9. doi: 10.1046/j.1365-2222.1998.00206.x.