title: IκB kinase-driven nuclear factor-κB activation in patients with asthma and chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Nuclear factor-κB (NF-κB) is a transcriptional factor of different inflammatory patterns involved in asthma and chronic obstructive pulmonary disease (COPD) that is tightly controlled by IκB kinase (IKK) complex.
  
  
  OBJECTIVE
  We investigated the dysregulation of IKK-driven NF-κB activation in patients with asthma and COPD.
  
  
  METHODS
  We assessed IKKα and IKKβ expression and activation, their regulation by glucocorticosteroids, and their involvement in IL-8 synthesis in PBMCs isolated from asthmatic patients, healthy smokers (HSs), patients with COPD, and control subjects. PBMCs from control subjects were stimulated with TNF-α and cigarette smoke extract in the presence or absence of fluticasone propionate (FP), L-glutathione reduced, or both, and IKK activation and IL-8 release were evaluated.
  
  
  RESULTS
  IKKα activity was higher in patients with COPD and HSs than in asthmatic patients and control subjects. IKKβ activity was higher in asthmatic patients, HSs, and patients with COPD than in control subjects. In vitro FP treatment induced inhibition of both IKKα and IKKβ activity in PBMCs from asthmatic patients, patients with COPD, and HSs, although IKKβ activity was more sensitive to FP than that of IKKα. FP reduced the IL-8 released from PBMCs of asthmatic patients, patients with COPD, and HSs, although IL-8 inhibition was higher in asthmatic patients than in patients with COPD and HSs. FP reduced IKKα and IKKβ activities in TNF-α and cigarette smoke extract-treated PBMCs, with higher levels of inhibition for IKKβ than IKKα activity. L-glutathione reduced improved the downregulatory effects of FP on IKKα and IL-8 levels.
  
  
  CONCLUSIONS
  Based on differential activation of IKKα and IKKβ, our findings suggest a different profile in the upstream regulation of the IKK-driven NF-κB system in asthmatic patients and patients with COPD. These differences in the regulation of the inflammatory process may explain, at least in part, the different pharmacologic responses in these patients.
authors.affiliation: Institute of Biomedicine and Molecular Immunology, Unit of Immunopathology and Pharmacology of Respiratory System, Italian National Research Council, Palermo, Italy. gagliardo@ibim.cnr.it
authors.forename: Rosalia
authors.initials: R
authors.lastname: Gagliardo
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
authors.forename: Mirella
authors.initials: M
authors.lastname: Profita
authors.forename: Anna
authors.initials: A
authors.lastname: Bonanno
authors.forename: Giusy Daniela
authors.initials: GD
authors.lastname: Albano
authors.forename: Angela Marina
authors.initials: AM
authors.lastname: Montalbano
authors.forename: Flora
authors.initials: F
authors.lastname: Pompeo
authors.forename: Cesare
authors.initials: C
authors.lastname: Gagliardo
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Merendino
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012907:Smoking
chemical_list: D001993:Bronchodilator Agents; D005938:Glucocorticoids; D016209:Interleukin-8; D016328:NF-kappa B; D051550:I-kappa B Kinase