title: The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages.
abstract: BACKGROUND
  Immune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder. The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells. We have previously published significant differences in peripheral blood mononuclear cell CB2R gene expression in the autism population. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls.
  
  
  METHODS
  To achieve these goals, we used biomolecular, biochemical and immunocytochemical methods.
  
  
  RESULTS
  GcMAF treatment was able to normalize the observed differences in dysregulated gene expression of the endocannabinoid system of the autism group. GcMAF also down-regulated the over-activation of BMDMs from autistic children.
  
  
  CONCLUSIONS
  This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism.
authors.affiliation: Department of Experimental Medicine, Second University of Naples, via S, Maria di Costantinopoli, 16 - 80138 Naples, Italy. dariosin@uab.edu.
authors.forename: Dario
authors.initials: D
authors.lastname: Siniscalco
authors.forename: James Jeffrey
authors.initials: JJ
authors.lastname: Bradstreet
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cirillo
authors.forename: Nicola
authors.initials: N
authors.lastname: Antonucci
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D001321:Autistic Disorder / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D063388:Endocannabinoids / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D016215:Macrophage-Activating Factors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014809:Vitamin D-Binding Protein / Q000494:pharmacology*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063388:Endocannabinoids; D016215:Macrophage-Activating Factors; D010739:Phospholipase D; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; D014809:Vitamin D-Binding Protein; D000099252:Fatty Acid Amide Hydrolases; C101908:vitamin D-binding protein-macrophage activating factor; C581518:NAPEPLD protein, human
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