title: CS1 (SLAMF7) inhibits production of proinflammatory cytokines by activated monocytes.
abstract: OBJECTIVE
  CS1 (CRACC, CD319, SLAMF7) is a member of the Signaling Lymphocyte Activation Molecule family expressed on immune cells mediating host defense. CS1 is a self-ligand and has both activating and inhibitory functions in Natural Killer cells. However, the function of CS1 in human monocytes is currently unknown. The objective of this study was to evaluate the control of CS1 surface expression in activated monocytes and to assess the effect of CS1 triggering on proinflammatory cytokine production by monocytes.
  
  
  METHODS
  Human monocytes were isolated from PBMC of healthy volunteers by magnetic depletion method or FACS sorting. The monocytes were cultured with or without LPS (1 μg/ml) in the presence or absence of various pharmacological inhibitors to inhibit NF-кB and PI3K signaling pathways. The cells were stimulated with anti-CS1 antibody or isotype control. Total RNA was extracted and RT-PCR was performed using specific primers for CS1 and EAT-2. Cell supernatants were collected and cytokine levels (TNF-α and IL-12p70) were determined by sandwich ELISA.
  
  
  RESULTS
  Our study revealed that adherent or LPS-activated monocytes express CS1, and CS1 induction is via NF-кB and PI3K pathways. Importantly, cross-linking CS1 resulted in reduced production of proinflammatory cytokines TNF-α and IL-12p70 by LPS-activated monocytes.
  
  
  CONCLUSIONS
  Our study demonstrated that CS1 plays an inhibitory role in human monocytes to control proinflammatory immune responses.
authors.affiliation: Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center at Fort Worth, TX 76107-2699, USA.
authors.forename: Jong R
authors.initials: JR
authors.lastname: Kim
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Horton
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Mathew
authors.forename: Porunelloor A
authors.initials: PA
authors.lastname: Mathew
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D008070:Lipopolysaccharides; D009000:Monocytes / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011971:Receptors, Immunologic / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D018664:Interleukin-12; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D014409:Tumor Necrosis Factor-alpha; C448987:SLAMF7 protein, human