Abstract Histamine, an important mediator in immediate-type hypersensitivity, is elevated in the skin of patients with atopic dermatitis and is considered to play a pathogenic role in atopic dermatitis. In this study, to elucidate the mechanism of sun exposure-induced exacerbation of skin lesions in atopic dermatitis, we examined the effect of histamine on proinflammatory cytokine production of keratinocytes induced by ultraviolet (UV) B irradiation. Cultured human keratinocytes were irradiated with 30 mJ/cm2 of UVB and incubated with histamine over the concentration range 10–7 to 10–4 M, and the IL-1α and IL-6 released into the medium were measured using an ELISA. Histamine weakly stimulated IL-6 production by itself. However, together with UVB, it synergistically enhanced IL-6 production and the amount of IL-6 mRNA as estimated by reverse-transcription polymerase chain reaction (RT-PCR). Histamine had a dose-dependent effect which was maximal at a concentration of 10–5 M, and had no effect on the kinetics of IL-6 production. In contrast, histamine had no effect on IL-1α production by keratinocytes. The effect of histamine was completely blocked by pyrilamine, an H1 receptor antagonist, and mimicked by the H1 receptor agonist, 2-methylhistamine. Whereas the H2 receptor antagonist, cimetidine, slightly inhibited the effect of histamine and the effect of the H2 receptor agonist, 4-methylhistamine, was minute. These results show that histamine augments UVB-induced IL-6 production by keratinocytes predominantly via the H1 receptor at the level of transcription. This suggests a contributory role for histamine in the exacerbation of atopic dermatitis induced by sun exposure.
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Received: 25 November 1997
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Shinoda, S., Kameyoshi, Y., Hide, M. et al. Histamine enhances UVB-induced IL-6 production by human keratinocytes. Arch Dermatol Res 290, 429–434 (1998). https://doi.org/10.1007/s004030050331
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DOI: https://doi.org/10.1007/s004030050331