Molecular cloning and characterization of a murine LPS-inducible cDNA.

CG Lee, J Demarquoy, MJ Jackson… - Journal of immunology …, 1994 - journals.aai.org
CG Lee, J Demarquoy, MJ Jackson, WE O'Brien
Journal of immunology (Baltimore, Md.: 1950), 1994journals.aai.org
Murine macrophages respond to endotoxins by inducing a vast array of genes that play a
major role in the host's response to infection and tumor growth. We have isolated and
characterized a 1.8-kb cDNA, designated IRG2, from a cDNA library prepared from RNA
isolated from the murine cell line, RAW 264.7, after bacterial LPS stimulation. The cDNA
encodes a protein of 47 kDa that is the murine homologue of a small family of proteins
described from IFN-induced human cells. The IRG2 message does not appear until 3 h after …
Abstract
Murine macrophages respond to endotoxins by inducing a vast array of genes that play a major role in the host's response to infection and tumor growth. We have isolated and characterized a 1.8-kb cDNA, designated IRG2, from a cDNA library prepared from RNA isolated from the murine cell line, RAW 264.7, after bacterial LPS stimulation. The cDNA encodes a protein of 47 kDa that is the murine homologue of a small family of proteins described from IFN-induced human cells. The IRG2 message does not appear until 3 h after LPS exposure and its induction is dependent on new protein synthesis. IRG2 induction by LPS is slightly inhibited by the anti-inflammatory steroid, dexamethasone. Increasing cytosolic cAMP with either forskolin, dibutyryl cAMP, or 8-(4-chlorophenylthio)-cAMP caused marked inhibition of the LPS induction of IRG2. In contrast, activation of PKC with phorbol ester potentiated the LPS response. Removing extracellular Ca2+ with EGTA inhibited IRG2 induction; increasing intracellular calcium with the calcium ionophore A23187 led to enhanced levels of the IRG2 transcript. These data suggest that the induction of IRG2 occurs via a PKC pathway.
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