bay-11-7082 and 2-3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine

Aminoacyl tRNA synthetase-interacting protein 1 (AIMP1) is a novel pleiotropic cytokine that was identified initially from Meth A-induced fibrosarcoma. It is expressed in the salivary glands, small intestine and large intestine, and is associated with the innate immune system. Previously, we demonstrated that AIMP1 might function as a regulator of innate immune responses by inducing the maturation and activation of bone-marrow-derived dendritic cells (BM-DCs). Toll-like receptors (TLRs) are major pathogen-recognition receptors that are constitutively expressed on DCs. In this study, we attempted to determine whether AIMP1 is capable of regulating the expression of TLRs, and also capable of affecting the TLR-mediated activation of DCs. Expression of TLR1, -2, -3 and -7 was highly induced by AIMP1 treatment in BM-DCs, whereas the expression of other TLRs was either down-regulated or remained unchanged. In particular, the expression of the TLR2 protein was up-regulated by AIMP1 in a time-dependent and dose-dependent manner, and was suppressed upon the addition of BAY11-7082, an inhibitor of nuclear factor-κB. AIMP1 was also shown to increase nuclear factor-κB binding activity. Importantly, AIMP1 enhanced the production of interleukin-6 and interleukin-12, and the expression of co-stimulatory molecules on BM-DCs when combined with lipoteichoic acid or Pam3Cys, two well-known TLR2 agonists. Collectively, these results demonstrate that the AIMP1 protein enhances TLR2-mediated immune responses via the up-regulation of TLR2 expression.

Topics: Animals; Antibodies, Monoclonal; CD40 Antigens; Cysteine; Cytokines; Dendritic Cells; DNA; Down-Regulation; Gene Expression; Immunity, Innate; Interleukin-12; Interleukin-6; Lipopolysaccharides; Lipoproteins; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-kappa B; Nitriles; Promoter Regions, Genetic; Protein Binding; Signal Transduction; Sulfones; Teichoic Acids; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors; Up-Regulation