TREM-1 expression in macrophages is regulated at transcriptional level by NF-kappaB and PU.1.
Triggering receptor expressed on myeloid cells (TREM)-1 is a recently identified immunoglobulin receptor that is expressed on neutrophils and monocytes where it amplifies the acute inflammatory response to bacteria. We examined the transcriptional regulation of TREM-1 in macrophages. Treatment of RAW cells with Escherichia coli LPS or Pseudomonas aeruginosa led to the induction of TREM-1 within 1 h with an expression lasting up to at least 24 h in vitro as detected by RT-PCR. Since the promoter of TREM-1 has multiple binding sites for NF-kappaB and PU.1 (one of the members of the ets family of transcription factors), we investigated the role of these transcription factors in the induction of TREM-1. Treatment of cells with NF-kappaB inhibitors abolished the expression of message of TREM-1 induced by LPS and P. aeruginosa. In contrast, the expression of TREM-1 was increased after stimulation with LPS or P. aeruginosa in cells that had gene of PU.1 silenced. Additionally, over-expression of PU.1 led to inhibition of TREM-1 induction in response to LPS and P. aeruginosa. These data suggest that both these transcription factors are involved in the expression of TREM-1. NF-kappaB functions as a positive regulator whereas PU.1 is a negative regulator of the TREM-1 gene.
Zeng
Heng
H
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, and Department of Veterans Affairs, Jesse Brown VA Hospital, Chicago, IL 60612, USA.
Ornatowska
Magdalena
M
Joo
Myung S
MS
Sadikot
Ruxana T
RT
D000818:Animals; D002460:Cell Line; D004926:Escherichia coli; D015870:Gene Expression / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D000099232:Proto-Oncogene Protein Spi-1
D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D015534:Trans-Activators; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D000099232:Proto-Oncogene Protein Spi-1; C517262:TREM1 protein, mouse