Increasing evidence suggests that TRIM family proteins may play important roles in the regulation of innate immune signaling pathways. Here we report TRIM22 is involved in the activation of NF-kappa B. It was found that overexpression of TRIM22 could dose-dependently activate NF-kappa B as demonstrated by reporter gene assay and electrophoretic mobility shift assay, but had no effect on the activity of other transcription factors, including NF-AT, AP-1, C/EBP and IRFs. Further study showed that both the N-terminal RING domain and C-terminal SPRY domain were crucial for TRIM22-mediated NF-kappa B activation. Moreover, our results revealed that TRIM22 overexpression could significantly induce the secretion of pro-inflammatory cytokines by human macrophage cell line U937 in an NF-kappa B-dependent manner. These data suggested that TRIM22 was a positive regulator of NF-kappa B-mediated transcription. (C) 2011 Elsevier Inc. All rights reserved.