title: In vitro modeling of COPD inflammation and limitation of p38 inhibitor - SB203580.
abstract: BACKGROUND
  Systemic inflammation and steroid resistance are the hallmarks of COPD. We examined the impact of p38 inhibitor (SB203580) in in vitro assays of systemic inflammation using pulmonary cells and patients' sera.
  
  
  OBJECTIVE
  Data from 66 COPD patients and 15 age-/sex-matched healthy controls were compared. Interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and CCL5 were measured in serum samples and culture media from peripheral blood mononuclear cells. The impact of sera on IL-10 and CCL5 expression in alveolar macrophage cell line (MH-S) was examined. The in vitro effects of SB203580 on lipopolysaccharide-induced inflammation were investigated.
  
  
  RESULTS
  Peripheral blood mononuclear cells from Global initiative for chronic Obstructive Lung Disease (GOLD) D patients produced more CCL5 and TNF-α, and less IL-10 compared to GOLD A-C patients. SB203580 treatment suppressed CCL5 and TNF-α and stimulated IL-10 production; however, the effect of SB203580 on IL-10 was lower in the COPD group. Culture of MH-S cells with COPD serum showed a significant increase in CCL5 and a significant decrease in IL-10 compared to healthy serum. This effect was not suppressed with SB203580 treatment.
  
  
  CONCLUSIONS
  COPD serum has a potent proinflammatory effect on pulmonary cells. Inhibition of p38 phoshorylation had a limited effect in restoring impaired lymphocyte function and suppressing inflammation induced by COPD serum, implying important p38-independent inflammatory mechanisms in COPD.
authors.affiliation: Respiratory Division, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, Peoples' Republic of China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Meng
authors.affiliation: Department of Thoracic Surgery, Hebei Province General Hospital, Shijiazhuang, Hebei, Peoples' Republic of China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Respiratory Division, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, Peoples' Republic of China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Wu
authors.affiliation: Respiratory Division, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, Peoples' Republic of China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Wu
authors.affiliation: Respiratory Division, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, Peoples' Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Respiratory Division, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, Peoples' Republic of China.
authors.forename: Xixin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors.forename: Kamilla
authors.initials: K
authors.lastname: Kopec-Harding
authors.affiliation: Centre for Respiratory and Allergy, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors.forename: Jiakai
authors.initials: J
authors.lastname: Wu
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D002460:Cell Line; D018946:Chemokine CCL5 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D016207:Cytokines; C508609:IL10 protein, human; D007093:Imidazoles; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: CCL5; COPD; IL-10; TNF-α; macrophage; p38MAPK inhibitor