Serum amyloid A (SAA) is a highly conserved, acute-phase protein synthesized predominantly by the liver, and has been thought to have a key role in the pathogenesis of rheumatoid arthritis, atherosclerosis, and secondary amyloidosis. We have recently observed that patients with psoriasis (n=25) have significantly higher level of SAA compared with healthy volunteers (n=17) or patients with atopic dermatitis (n=14). Furthermore, the SAA protein level in the sera of patients with psoriasis significantly correlated with Psoriasis Area and Severity Index scores (N=31, the Spearman rank correlation coefficient=0.4388867, P<0.01). We next sought molecular mechanisms that might explain the SAA increase in patients with psoriasis and hypothesized that some inflammatory cytokines expressed in psoriatic lesions induce SAA expression in keratinocytes. We stimulated normal human epidermal keratinocytes (NHEKs) with panels of inflammatory cytokines, and the analyses using real-time PCR and ELISA revealed that the Th1 cytokine IFN-gamma (50 ng/ml), the Th17 cytokine IL-17A (50 ng/ml), and TNF-alpha (50 ng/ml) significantly induced SAA expression in NHEKs, but the Th2 cytokines IL-4 (50 ng/ml) and IL-13 (50 ng/ml) did not. In addition, antimicrobial peptides including human beta defensin 2 (HBD2, 10-6 M), HBD3 (10-6 M), and LL-37(10-6 M) which are highly expressed in psoriatic skin, also significantly induced SAA expression in NHEKs. Furthermore, SAA induced SAA itself and IL-36 gamma expression in a dose-dependent manner (10-8 – 10-6 M) in NHEKs, and siRNA-mediated gene silencing and neutralizing antibodies clarified that the inductions were mediated by Toll-like receptor 1/2. These results suggest that psoriatic skin inflammation would contribute to the elevation of SAA in the sera of psoriasis patients, which might trigger systemic complications.