The Receptor CMRF35-Like Molecule-1 (CLM-1) Enhances the Production of LPS-Induced Pro-Inflammatory Mediators during Microglial Activation
Ejarque-Ortiz, Aroa (Hospital Universitari Vall d'Hebron)
Solà, Carme (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Martínez-Barriocanal, Águeda (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Schwartz, Simon (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martín, Margarita (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Peluffo, Hugo (Institut Pasteur de Montevideo)
Sayós, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2015
Resum:	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.
Ajuts:	Ministerio de Ciencia e Innovación PI1100045 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-493
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 10 (april 2015) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0123928
PMID: 25927603

17 p, 3.6 MB

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