title: Vitamin D3 Treatment Decreases Frequencies of CD16-Positive and TNF-α-Secreting Monocytes in Asthmatic Patients.
abstract: BACKGROUND
  Previously, we demonstrated that glucocorticoid (GC) treatment of asthmatic patients resulted in decreasing frequencies of monocyte subsets expressing CD16 and capable of releasing TNF-α. Here, we wished to analyze whether the active form of vitamin D, i.e. vitamin D3, referred to as 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16-positive monocytes and thus decrease the proinflammatory potential of these cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3 would facilitate the use of lower doses of GC without decreasing their anti-inflammatory properties.
  
  
  METHODS
  Peripheral blood mononuclear cells collected from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3 and/or varying doses of GC in the presence or absence of caspase inhibition. The cells were either directly stained for extracellular markers or prestimulated with lipopolysaccharide for the assessment of intracellular cytokine production and then analyzed by flow cytometry.
  
  
  RESULTS
  We found that 1,25-(OH)2D3 alone (and in combination with GC) decreased the frequency of CD14++CD16+ and CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF-α production by the monocytes. With regard to the CD14+CD16++ subset, the monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan-caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action. Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory effects.
  
  
  CONCLUSIONS
  This study has revealed novel immunomodulatory properties of 1,25-(OH)2D3 directed against monocyte subsets capable of TNF-α production. In addition, our data suggest that the introduction of 1,25-(OH)2D3 to anti-inflammatory therapy would possibly allow for the use of lower doses of GC.
authors: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors: Kamil
authors: K
authors: Grubczak
authors: Danuta
authors: D
authors: Lipinska
authors: Andrzej
authors: A
authors: Eljaszewicz
authors: Paulina
authors: P
authors: Singh
authors: Urszula
authors: U
authors: Radzikowska
authors: Paula
authors: P
authors: Miklasz
authors: Milena
authors: M
authors: Dabrowska
authors: Ewa
authors: E
authors: Jablonska
authors: Anna
authors: A
authors: Bodzenta-Lukaszyk
authors: Marcin
authors: M
authors: Moniuszko
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D061945:Caspase Inhibitors / Q000627:therapeutic use; D002762:Cholecalciferol / Q000627:therapeutic use*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D061945:Caspase Inhibitors; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D005938:Glucocorticoids; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol