title: [Effect of selective phosphodiesterase 4 inhibitors on nuclear factor kappa B, tumor necrosis factor-α and interleukin-8 expression in peripheral blood mononuclear cells in rheumatoid arthritis with interstitial lung disease].
abstract: OBJECTIVE
  To investigate the effect of selective phosphodiesterase (PDE) 4 inhibitors on nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNFα) and interleukin-8 (IL-8) secreted by peripheral blood mononuclear cells (PBMCs) in patients diagnosed as rheumatoid arthritis with interstitial lung disease (RA-ILD).
  
  
  METHODS
  PBMCs isolated from 15 healthy volunteers (group A) and 20 patients with untreated active RA-ILD (group B) were cultured in vitro. PBMCs from healthy subjects were considered as normal control. PBMCs from RA-ILD patients were divided into four groups with different treatment: blank group (B1), theophylline group (B2), selective PDE4 inhibitor rolipram group (B3), and glucocorticoid group (B4) with dexamethasone. The expression of NF-κB was determined by immunocytochemical staining, and the levels of TNFα and IL-8 in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA).
  
  
  RESULTS
  (1) The activity of NF-κB and the levels of TNFα and IL-8 in group B1 were significant higher than that in group A (P < 0.01). Compared with group B1, three parameters above were similar to those in group B2 (P > 0.05), while group B3 and group B4 had significant decreased levels of three parameters (P < 0.01); IL-8 level in group B4 was significantly lower than that in group B3 (P < 0.05). (2) TNFα and IL-8 levels were positively correlated with NF-κB activity in group B (r = 0.902 and 0.735, P < 0.01 respectively). (3) The reduction of TNFα and IL-8 levels were positively correlated with reduction of NF-κB activity after intervention of rolipram in group B3 (r = 0.874, P < 0.01; r = 0.561, P < 0.05 respectively).
  
  
  CONCLUSIONS
  NF-κB activation and proinflammatory cytokines were involved in the pathogenesis of RA-ILD. selective PDE4 inhibitors may inhibit the production of inflammatory cytokines by inhibiting the activity of the transcription factor NF-κB in PBMC, thus inhibiting the inflammatory reaction of RA-ILD.
authors.affiliation: Department of Respiratory Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China. Email:songning1972@qq.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.forename: Ai-jing
authors.initials: AJ
authors.lastname: Liu
authors.forename: Xue-feng
authors.initials: XF
authors.lastname: Gao
authors.forename: Xian-li
authors.initials: XL
authors.lastname: Guo
authors.forename: Ji-tao
authors.initials: JT
authors.lastname: Guan
authors.forename: Jian-ling
authors.initials: JL
authors.lastname: Wu
authors.forename: Rui-fang
authors.initials: RF
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Duan
authors.forename: Wen-shu
authors.initials: WS
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D058988:Phosphodiesterase 4 Inhibitors; D014409:Tumor Necrosis Factor-alpha