Identification of an endotoxin and IFN-inducible cDNA: possible identification of a novel protein family.

The response of macrophages to agents such as lipopolysaccharide (LPS) and interferon (IFN) includes the transcriptional activation of numerous genes. We have used the method of differential screening of a RAW 264.7 macrophage cell line cDNA library to isolate and characterize LPS-induced messages. One such message, LRG-47, is induced by LPS, IFN-gamma, and IFN-alpha/beta, but not by a panel of other cytokines or pharmacological activating agents. LRG-47 is homologous to two other IFN-gamma-induced genes, IRG-47 and Mg21. The LRG-47 sequence is approximately 33% identical and 52% similar to both these putative protein products. All three putative proteins, particularly Mg21, bear homology to a T cell product, Tgtp, induced by T cell receptor cross-linking. The three macrophage-derived proteins share areas of homology with GTP-binding proteins, are approximately 415 amino acids in length, and have similar kinetics of induction by IFN-gamma. This suggests that these genes may be members of a new family of IFN-inducible proteins.