Corticosteroids induce proliferation but do not influence TNF- or IL-1?-induced ICAM-1 expression of human dermal microvascular endothelial cells in vitro

Abstract

The effects of hydrocortisone, dexamethasone, betamethasone 17-valerate and clobetasol propionate at concentrations of 10(-5)-10(-12) M on the proliferation of human dermal microvascular endothelial cells (HDMEC) were studied in vitro. In addition, confluent HDMEC were treated with TNF (1000 U/ml) or IL-1 beta (1000 U/ml) alone or in combination with the corticosteroids (10(-5) M, 10(-6) M) for 24 h, and cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1) was assessed by immunocytochemistry. Controls were treated either with growth medium or with the corticosteroids alone. All tested corticosteroids stimulated HDMEC growth after 4 and 6 days of treatment in a dose-dependent manner, as assessed by 3H-thymidine incorporation and the 4-methyl-umbelliferyl heptanoate (MUH) assay. The minimal effective concentration was 10(-9) M for hydrocortisone, 10(-10) M for dexamethasone and betamethasone, and 10(-12) M for clobetasol. In untreated and in corticosteroid-treated cultures, less than 5% of the cells expressed ICAM-1. TNF and IL-1 beta were strong inducers of ICAM-1 expression on 74% and 82% of the cells, respectively. None of the tested corticosteroids significantly influenced cytokine-induced ICAM-1 expression, suggesting that the anti-inflammatory effects of corticosteroids are not related to ICAM-1 modulation on HDMEC.

Adverse effects of topical glucocorticosteroids

“…In addition to atrophy, corticosteroids stimulate human dermal microvascular endothelial cells, 41 leading to the occurrence of telangiectasia. This condition is characterized by an abnormal dilatation of capillary vessels and arterioles.…”

Expression of Adhesion Molecules in Cultured Human Nasal Mucosal Microvascular Endothelial Cells Activated by Interleukin–1â or Tumor Necrosis Factor–·: Effects of Dexamethasone

“…Several reports have investigated the effect of glucocorticoid on adhesion molecule expression in microvascular ECs. In human dermal EC in vitro, glucocorticoids did not influence TNF–α– or IL–1β–induced ICAM–1 expression [38]. The expression of E–selectin on synovial blood vessels in patients with rheumatoid arthritis decreased after administration of methylprednisolone acetate [39].…”

Combination Therapy Improves the Recovery of the Skin Barrier Function: An Experimental Model Using a Contact Allergy Patch Test Combined with TEWL Measurements

“…The barrier properties of the moisturizing cream used in this study might have played a role in the penetration of the topical corticosteroids. As a result, an increase in the anti-inflammatory effect of topical corticosteroids on the dermal level was noted: depletion of CD and HLA-DR molecules on Langerhans cells [16], inhibition of IL-2, TNF-γ [17]and arachidonic acid [18], release and inhibition of the production of IL-1 and TNF-α [19]. The synergetic phenomenon observed in skin barrier healing, when the topical corticosteroid was combined with barrier cream application, is also related to the effectiveness of the latter in restoring an abnormal barrier function [20].…”