The Receptor CMRF35-Like Molecule-1 (CLM-1) Enhances the Production of LPS-Induced Pro-Inflammatory Mediators during Microglial Activation.
CMRF35-like molecule-1 (CLM-1) belongs to a receptor family mainly expressed in myeloid cells that include activating and inhibitory receptors. CLM-1 contains two ITIMs and a single immunoreceptor tyrosine-based switch motif (ITSM), although also displays a binding site for p85α regulatory subunit of PI3K. By using murine primary microglial cultures, we show the presence of all CLM members in microglial cells and characterize the expression of CLM-1 both in basal conditions and during microglial activation. The TLR4 agonist lipopolysaccharide (LPS) and the TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) induce an increase in microglial CLM-1 mRNA levels in vitro, whereas the TLR2/6 heterodimer agonist peptidoglycan (PGN) produces a marked decrease. In this study we also describe a new soluble isoform of CLM-1 that is detected at mRNA and protein levels in basal conditions in primary microglial cultures. Interestingly, CLM-1 engagement enhances the transcription of the pro-inflammatory mediators TNFα, COX-2 and NOS-2 in microglial cells challenged with LPS. These results reveal that CLM-1 can acts as a co-activating receptor and suggest that this receptor could play a key role in the regulation of microglial activation.
Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain.
Aroa
A
Ejarque-Ortiz
Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Carme
C
Solà
Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain.
Águeda
Á
Martínez-Barriocanal
Drug Delivery and Targeting Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain.
Simó
S
Schwartz
Biochemistry Unit, Faculty of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Margarita
M
Martín
Neurodegeneration Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay.
Hugo
H
Peluffo
Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain.
Joan
J
Sayós
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D041681:NIH 3T3 Cells; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D051546:Cyclooxygenase 2; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D011070:Poly I-C; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C482560:CLM-1 protein, mouse; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse