Macrophage migration is controlled by Tribbles 1 through the interaction between C/EBPβ and TNF-α

In mammals, three Tribbles gene family members have been identified, Tribbles 1, 2 and 3 (Trib1,Trib2 and Trib3). All family members are considered to be pseudokinases in that they contain domains homologous to serine/threonine kinase catalytic cores, but they lack several conserved residues in the ATP-binding pocket. Trib1 is implicated in the inflammatory response pathway through its ability to regulate mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-kappa B) and CCAAT Enhancer Binding Protein (C/EBP). However, its role in macrophages function is unknown. Here, we investigated the functional role of Trib1 in Toll-like receptor-mediated inflammatory responses to IFN-gamma in RAW264.7 cells. In gene knock-down experiments in macrophages using small interfering RNAs targeted to Trib1, it was observed that TNF-alpha production was increased following treatment with IFN-gamma and/or TLR2 ligands. Finally, Trib1-silenced macrophages failed to show MCP-1 induced chemokinesis and indicating involvement of Trib1 in controlling of macrophage migration. This work demonstrates that Trib1 contributes to the pro-inflammatory response caused by TLR2 ligands and controls macrophage migration as well as being a biomarker in macrophage-related diseases in both human and veterinary medicine. (C) 2013 Elsevier B.V. All rights reserved.