Histamine enhances UVB-induced IL-6 production by human keratinocytes.
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-1alpha 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-1alpha 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.
Department of Dermatology, Hiroshima University School of Medicine, Japan.
S
S
Shinoda
Y
Y
Kameyoshi
M
M
Hide
E
E
Morita
S
S
Yamamoto
D000328:Adult; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000528:radiation effects*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D006632:Histamine