title: Toll-like receptor 3 and interleukin 1β expression in CD34+ cells from patients with rheumatoid arthritis: association with inflammation and vascular involvement.
abstract: OBJECTIVE
  Circulating proangiogenic haematopoietic cells (PHCs), including CD34+ cells, play an important role in endothelial homeostasis. Among PHCs, CD34+ cells are the largest cell population, thus, much of the regenerative/reparative potential of PHCs may be attributed to CD34+ cells. Our aim was to determine the association between inflammation and CD34+ cell number, intracellular levels of reactive oxygen species (ROS) and expression of Toll-like receptor 3 (TLR3) and interleukin 1β (IL-1β), arterial stiffness (AS) indices, and carotid intima-media thickness (cIMT) in patients affected by rheumatoid arthritis (RA).
  
  
  METHODS
  CD34+ cells were isolated from 24 RA patients and 26 matched controls. ROS levels, TLR3 and IL-1β expression were measured. C-reactive protein (CRP), fibrinogen, AS, and cIMT were also evaluated.
  
  
  RESULTS
  CD34+ count was lower in RA patients as compared to controls. In CD34+ cells from RA patients, ROS, TLR3 and IL-1β expressions were increased compared to controls. In RA patients, we found higher CRP and fibrinogen levels, and higher values of Pulse Wave Velocity (PWV) and Augmentation Index (AIx), both AS indices, and of cIMT. CD34+ cell numbers were inversely correlated with CRP, TLR3, IL-1β, ROS, and AS indices. TLR3 levels were related to CRP, IL-1β, fibrinogen and ROS. IL-1β levels were correlated with expression of CRP, ROS, and PWV.
  
  
  CONCLUSIONS
  Inflammatory status in RA is associated with an increased expression of TLR3 and of IL-1β in CD34+ cells, which appear to affect cell number. These new findings suggest a perspective on accelerated atherosclerosis and vascular damage in RA.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy. albertologullo@virgilio.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lo Gullo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mandraffino
authors.forename: Egidio
authors.initials: E
authors.lastname: Imbalzano
authors.forename: Federica
authors.initials: F
authors.lastname: Mamone
authors.forename: Caterina Oriana
authors.initials: CO
authors.lastname: Aragona
authors.forename: Angela
authors.initials: A
authors.lastname: D'Ascola
authors.forename: Saverio
authors.initials: S
authors.lastname: Loddo
authors.forename: Antonella
authors.initials: A
authors.lastname: Cinquegrani
authors.forename: Angela
authors.initials: A
authors.lastname: Alibrandi
authors.forename: Enricomaria
authors.initials: E
authors.lastname: Mormina
authors.forename: Gianfilippo
authors.initials: G
authors.lastname: Bagnato
authors.forename: Renato
authors.initials: R
authors.lastname: Lo Gullo
authors.forename: Maria Adriana
authors.initials: MA
authors.lastname: Sardo
authors.forename: Antonino
authors.initials: A
authors.lastname: Saitta
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D015854:Up-Regulation; D059289:Vascular Stiffness
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C508585:IL1B protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D002097:C-Reactive Protein