title: Deregulation of the IL-1β axis in chronic recurrent multifocal osteomyelitis.
abstract: BACKGROUND
  This study aims to investigate the inflammasome response in peripheral blood mononuclear cells (PBMCs) and the expression of inflammasome components in bone biopsies from patients with chronic recurrent multifocal osteomyelitis (CRMO).
  
  
  METHODS
  The expression of inflammasome components mRNAs was evaluated in PBMCs isolated from 15 CRMO patients and 13 healthy controls by quantitative real-time PCR. The Interleukin (IL)-1β released in the medium of PBMC cultures after treatment with lipopolysaccharides (LPS) alone or LPS and ATP was measured by ELISA. Immunohistochemical staining for Apoptosis-associated Speck-like protein (ASC), caspase-1 (CASP-1), Nod-like receptor protein-3 (NLRP3) and IL-1β expression was performed in bone biopsies from CRMO patients.
  
  
  RESULTS
  mRNA levels of ASC, CASP-1 and IL-1β were significantly higher in freshly isolated PBMCs from CRMO patients in active disease than in healthy controls. CASP-1 and IL-1β transcript levels were significantly higher also in PBMCs from CRMO patients in remission compared to healthy controls. PBMCs from CRMO patients in active disease stimulated in vitro with LPS showed a significant increase in IL-1β release compared to healthy control cells. Immunohistochemistry staining of bone tissue revealed the expression of inflammasome components in CRMO osteoclasts.
  
  
  CONCLUSIONS
  Our data suggest that an abnormal regulation of IL-1β axis may be involved in CRMO pathogenesis.
authors: Rheumatology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Roberta
authors: R
authors: Scianaro
authors: Rheumatology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Antonella
authors: A
authors: Insalaco
authors: Rheumatology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Luisa
authors: L
authors: Bracci Laudiero
authors: Division of Pathology, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Rita
authors: R
authors: De Vito
authors: Core Facilities, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Marco
authors: M
authors: Pezzullo
authors: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors: Anna
authors: A
authors: Teti
authors: Rheumatology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Fabrizio
authors: F
authors: De Benedetti
authors: Rheumatology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Giusi
authors: G
authors: Prencipe
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000235:genetics; D001706:Biopsy; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010019:Osteomyelitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D062072:Patient Acuity; D015398:Signal Transduction / Q000235:genetics
chemical_list: D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C402202:PYCARD protein, human; D020170:Caspase 1
keywords: Autoinflammatory disorders; Chronic recurrent multifocal osteomyelitis; Inflammasome; Interleukin-1β; Osteoclasts