Asunto(s)
Alérgenos/sangre , Dermatitis Atópica/inmunología , Níquel/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Alérgenos/inmunología , Suplementos Dietéticos , Femenino , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Níquel/sangre , Factores Sexuales , Balance Th1 - Th2 , Adulto JovenRESUMEN
Nickel (Ni) ions easily elute from many alloys and elicit inflammation and allergies. Previous studies have shown that infections due to the implantation of medical devices cause inflammation and enhance the elution of Ni ions (Ni²âº). However, cross-talk between infection- and Ni²âº-induced signaling pathways has not yet been elucidated in detail. In the present study, we investigated the effects of Ni2+ on the lipopolysaccharide (LPS)-induced production of cytokines in a LPS-induced air pouch-type inflammation model in BALB/c mice and the murine macrophage cell line RAW264. We demonstrated that Ni²âº inhibited the LPS-induced production of interleukin (IL)-6, but not that of tumor necrosis factor (TNF)-α both in vivo and in vitro. This inhibitory effect was also observed with cobalt ion (Co²âº), but not with chloride ion (Clâ»), zinc ion (Zn²âº), or palladium ion (Pd²âº), and was highly selective to the production of IL-6. Ni²âº did not inhibit the activation of ERK1/2, p38 MAPK, or JNK. Although Ni²âº decreased IL-6 mRNA levels, it failed to inhibit the LPS-induced activation of the IL-6 promoter. An experiment using actinomycin D, a transcription inhibitor, revealed that Ni²âº decreased the stability of IL-6 mRNA. Moreover, Ni²âº inhibited the LPS-induced expression of Arid5a, but not regnase-1. These results demonstrated that Ni²âº may have selectively inhibited the LPS-induced production of IL-6 by decreasing the Arid5a-dependent stabilization of IL-6 mRNA.