title: Immune receptor expressed on myeloid cells 1 (IREM-1) inhibits B cell activation factor (BAFF)-mediated inflammatory regulation of THP-1 cells through modulation of the activities of extracellular regulated kinase (ERK).
abstract: The immune receptor expressed on myeloid cells 1 (IREM-1) has been known to regulate the activities of myeloid cells through its immunoreceptor tyrosine-based inhibition motifs (ITIMs) in its intracellular region. In order to investigate its effect on macrophage activation, a human macrophage cell line (THP-1) was tested after stimulation of its membrane-bound form of B cell activation factor (BAFF), which has been shown to modulate inflammatory activities through induction of proinflammatory mediator expression and suppression of phagocytosis. IREM-1-specific monoclonal antibodies detected the expression of high levels of IREM-1 in THP-1 cells. Cross-linking of IREM-1 with these antibodies resulted in the blockage of the BAFF-mediated expression of interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 through inhibition of the activation of extracellular regulated kinase (ERK) and phosphorylation/degradation of IκB. Furthermore, cross-linking of IREM-1 also reversed the BAFF-mediated inhibition of phagocytosis. In order to demonstrate the role of ITIM in the IREM-1-mediated suppression of BAFF signalling, a decapeptide containing YADL (an ITIM in IREM-1) was fused with HIV-TAT(48-57) which was required for the internalization of the synthetic polypeptide (TAT-YADL). TAT-YADL, but not control peptides, recapitulated the effect of the anti-IREM-1 monoclonal antibody. These observations indicate that IREM-1 exerted its inhibitory effect on BAFF-medicated signalling through ITIM-mediated regulation of ERK activities in THP-1 cells.
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Korea.
authors.forename: S-M
authors.initials: SM
authors.lastname: Lee
authors.forename: Y-P
authors.initials: YP
authors.lastname: Nam
authors.forename: K
authors.initials: K
authors.lastname: Suk
authors.forename: W-H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D020298:U937 Cells
chemical_list: D000911:Antibodies, Monoclonal; D053264:B-Cell Activating Factor; C519443:CD300LF protein, human; D016209:Interleukin-8; D009842:Oligopeptides; D011971:Receptors, Immunologic; C505719:TNFSF13B protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D020780:Matrix Metalloproteinase 9