Allicin Inhibited IL-17A-activated TRAF6/MAPK and STAT3/NF-κB Signaling Pathways in Vitro and in Vivo
It has been confirmed that activated IL‑17A signaling recruits TRAF6, which leads to simultaneous activation of the NF-κB by MAPK phosphorylation(Kobayashi et al. , 2003). Topical application of IMQ induces IL-17-mediated psoriatic dermatitis via TRAF6 signaling. In addition, IL-17-enhanced NF-κB transcriptional activity in keratinocytes was stimulated by the activation of STAT3 and NF-κB pathways. We next co-cultured keratinocytes with IL-17A with or without allicin, then further detected the activation of TRAF6, ERK1/2, P38, JNK, STAT3, and P65. Figure 8A showed that IL-17A stimulation for 30 min effectively upregulated the phosphorylation expression of ERK1/2, P38, JNK, and P65 in HaCaT cells, while treatment with allicin significantly inhibited the protein expression of TRAF6 and MAPK and restrained the phosphorylation of MAPK, STAT3, and P65 (Figure 8B, 8C). To investigate whether allicin alleviates IMQ-induced psoriatic lesions by inhibiting downstream pathways activated by IL-17A, we analyzed the protein expressions of TRAF6/MAPK/STAT3/NF-κB, which were significantly repressed in IMQ-induced psoriatic lesions (Figure 8D, 8E). Overall, the results showed that allicin could inhibit inflammation by suppressing the activation of IL-17A downstream signaling pathways (Figure 8F).