A20 and ABIN-3 possibly promote regression of trehalose 6,6'-dimycolate (TDM)-induced granuloma by interacting with an NF-kappa B signaling protein, TAK-1.

The objective of this paper is to examine the role of NF-kappa B inhibitors A20 and ABIN-family proteins in the trehalose 6,6'-dimycolate (TDM)-induced model of tuberculous granulomatous lesions. BALB/c mice were twice injected i.p. with w/o/w emulsions that contain TDM at a 1 week-interval. The mice were killed at days 0, 3, 7, 14, or 21 after the last injection. The mRNA and protein levels of A20 and ABIN-family proteins were measured by real-time PCR using mRNA or protein extract from the lesions. The activation status of NF-kappa B was analyzed by Western blotting and immunohistochemistry. Finally, the protein extracts were immunoprecipitated by anti-ABIN-3 antibody to identify the protein that potentially interacts with ABIN-3. The activation of NF-kappa B pathway coincided with granuloma development, while A20 and ABIN-3 increased in accordance with granuloma regression. TAK-1 protein was co-precipitated with ABIN-3 by immunoprecipitation using anti-ABIN-3 antibody. The results suggest that ABIN-3 contributed to granuloma regression by interacting with TAK-1 and, as a consequence, inhibiting activation of NF-kappa B pathway.