The aetiology of vitiligo remains unclear. An autoimmune involvement has been suggested and, in this study, we examine whether melanocytes cultured from unaffected regions of the skin of vitiligo patients are more susceptible to immune attack by investigating constitutive and cytokine-stimulated expression of intercellular adhesion molecule-1 (ICAM-1) (under three media variants) and major histocompatibility complex (MHC) class I and class II (under one medium). Both normal and vitiligo melanocytes had similarly low constitutive expression of ICAM-1 and MHC class II molecules, whereas > 95% of cells had high constitutive expression of MHC class I. Normal and vitiligo melanocytes showed similar and significant increases in the expression of all three immune-related molecules in response to the cytokine, interferon-gamma. The expression of ICAM-1 was also similarly increased by the cytokine, tumour necrosis factor-alpha in both cells. Additionally, it was noted that, once the melanocyte cultures were established under experimental conditions, the rate of proliferation of vitiligo melanocytes did not differ significantly from that of normal melanocytes. In conclusion, we suggest that vitiligo melanocytes, once in culture, do not have intrinsic differences from normal melanocytes with respect to the expression of immune-related molecules.

The aims of this study were to investigate whether keratinocytes are capable of playing a direct preimmune role in the pathophysiology of allergic contact dermatitis (ACD) and to examine to what extent the degree of differentiation might influence this. We measured the ability of sensitizing agents to up-regulate intercellular adhesion molecule 1 (ICAM-1) expression in cultured normal human keratinocytes (NHK) and in the transformed human keratinocyte HaCaT cell line. In proliferative HaCaT cells, following a 24 h exposure, nickel compounds, para-phenylenediamine (pPD) and 1-chloro-2,4-dinitrobenzene produced a concentration-dependent up-regulation of ICAM-1 expression without reducing cell viability, while K2Cr2O7 led to ICAM-1 up-regulation at cytotoxic concentrations, and CrCl3 was without effect. In NHK, NiSO4 and pPD induced ICAM-1 expression to a significantly greater extent in proliferative cells than in differentiated cells, where involucrin expression was measured to assess the differentiation state. NiSO4- or pPD-pretreatment of proliferative HaCaT cells enhanced T-cell binding, which was abolished by neutralizing antibodies to ICAM-1 or CD18. Our investigations concerning the involvement of oxidative stress in the induction of ICAM-1 expression in response to sensitizing agents were inconclusive. The oxidizing agents FeCl3 and H2O2 up-regulated ICAM-1 expression in HaCaT cells but there was no clear relationship between the ability of agents to induce ICAM-1 expression and their ability to alter the levels of reduced glutathione. Although pPD increased interleukin-1 alpha release from NHK, this cytokine was not capable of inducing ICAM-1 expression in NHK. Tumour necrosis factor-alpha, which does induce ICAM-1 expression in NHK, was not detected in response to pPD, arguing against an autocrine pathway of ICAM-1 induction in response to pPD. In summary, we report the direct interaction of sensitizing agents with keratinocytes leading to the generation of immune signals, particularly by proliferative keratinocytes, suggesting an active role for the proliferative keratinocyte in the pathophysiology of ACD.

No abstract

No abstract