cord-factors and Peritoneal-Diseases

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.

Topics: Adaptor Proteins, Signal Transducing; Animals; Cord Factors; Cysteine Endopeptidases; DNA-Binding Proteins; Female; Granuloma; Intracellular Signaling Peptides and Proteins; MAP Kinase Kinase Kinases; Mice; Mice, Inbred BALB C; NF-kappa B; Nuclear Proteins; Omentum; Peritoneal Diseases; RNA, Messenger; Tumor Necrosis Factor alpha-Induced Protein 3; Ubiquitin-Protein Ligases

When spread as a monolayer on the surface of hydrophobic beads and injected into mice, the mycobacterial glycolipid, trehalose 6,6'-dimycolate, reproduces the biologic effects traditionally associated with virulent mycobacteria, including acute inflammation, granuloma formation, and immune adjuvancy. Repeated intraperitoneal injection of glycolipid-coated beads into young C57Bl/6 mice elicits a granulomatous peritonitis, with concomitant dissemination of beads from the peritoneum to distant organs. Glycolipid-coated beads which disseminate from the peritoneum to other sites elicit neither acute inflammation nor granulomata. The coagulation system may be involved in the dissemination of glycolipid-coated beads as evidenced by the following: fibrinogen is a necessary cofactor of the trehalose dimycolate monolayer; diffuse peritoneal and pulmonary hemorrhage accompanies bead dissemination; peritoneal exudate collected shortly after intraperitoneal injection of glycolipid-coated beads is enriched in coagulant activity; coagulability of blood from trehalose dimycolate-treated animals is reduced; and anticoagulation inhibits the inflammatory response to glycolipid-coated beads. In this report, the dissemination of trehalose dimycolate-coated beads is characterized, and a role for the coagulation system in this process is proposed.

Topics: Animals; Blood Coagulation; Cord Factors; Glycolipids; Granuloma; Inflammation; Leukocytes; Lymphatic Diseases; Mice; Microspheres; Peritoneal Diseases; Polystyrenes; Time Factors; Tissue Adhesions; Tissue Distribution