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Published on: May 31, 2018
Modulation of melanocyte intercellular adhesion molecule-1 by immune cytokines
J J Yohn1, M Critelli, M B Lyons
1Department of Dermatology, University of Colorado School of Medicine, Denver.
Insights
Human melanocytes express intercellular adhesion molecule-1 (ICAM-1), which increases with stimulation by interferon gamma (IFN-G), tumor necrosis factor alpha (TNF-alpha), or interleukin-1-alpha (IL-1 alpha). This finding aids understanding of immune-mediated melanocyte injury.
Area of Science:
- Immunodermatology
- Cellular Immunology
- Molecular Biology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) plays a crucial role in immune cell interactions.
- Melanocytes, the pigment-producing cells of the skin, are involved in immune responses.
- Understanding ICAM-1 expression on melanocytes is important for investigating immune-mediated skin conditions.
Purpose of the Study:
- To investigate the expression of ICAM-1 on human melanocytes.
- To determine the effect of key cytokines (IFN-G, TNF-alpha, IL-1 alpha) on melanocyte ICAM-1 expression.
- To establish the dose-dependency and potential synergy of cytokine-induced ICAM-1 expression.
Main Methods:
- Direct immunofluorescence and fluorescence-activated cell sorting (FACS) were used to quantify ICAM-1 expression.
- Human melanocytes cultured in vitro were exposed to varying concentrations of IFN-G, TNF-alpha, and IL-1 alpha.
- Dose-response relationships and additive effects of combined cytokines were analyzed.
Main Results:
- In vitro cultured melanocytes expressed low basal levels of ICAM-1.
- IFN-G, TNF-alpha, and IL-1 alpha significantly upregulated melanocyte ICAM-1 expression in a dose-dependent manner.
- Melanocytes showed the highest sensitivity to TNF-alpha; combined cytokines resulted in additive, not synergistic, increases in ICAM-1.
Conclusions:
- This study is the first to report ICAM-1 induction on melanocytes by TNF-alpha and IL-1 alpha, and by physiologically relevant doses of IFN-G.
- Cytokine-mediated ICAM-1 expression on melanocytes has implications for immune cell-target interactions.
- Further research into melanocyte ICAM-1 may elucidate immune mechanisms underlying melanocyte injury.
Abstract:
Human melanocyte expression of intercellular adhesion molecule-1 (ICAM-1) with or without stimulation by interferon gamma (IFN-G), tumor necrosis factor alpha (TNF-alpha), or interleukin-1-alpha (IL-1 alpha), was measured utilizing direct immunofluorescence and fluorescence-activated cell sorting (FACS). Melanocytes grown in vitro expressed low levels of ICAM-1, which could be increased by exposing the cells to IFN-G, TNF-alpha, or IL-1 alpha. Each cytokine caused an enhancement of melanocyte ICAM-1 expression in a dose-dependent fashion. The lowest dose necessary to cause a significant increase in melanocyte ICAM-1 expression was 1 U/ml IFN-G, 0.3 ng/ml TNF-alpha, or 3 U/ml IL-1 alpha. Melanocytes were most sensitive to TNF-alpha stimulation, with the greatest levels of ICAM-1 expression following 30 ng/ml or more TNF-alpha. When IFN-G was added to melanocyte cultures in combination with TNF-alpha or IL-1 alpha, there was an additive increase in ICAM-1 expression but no synergy was noted with the combined cytokines. To our knowledge, this is the first report of melanocyte ICAM-1 induction by TNF-alpha and IL-1 alpha and by physiologically relevant doses of IFN-G. Because of the importance of ICAM-1 in the regulation of immune cell-target interactions, the study of ICAM-1 expression by melanocytes may help us to better understand immune mechanisms of melanocyte injury.
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