title: Tumor necrosis factor alpha (TNF-α) autoregulates its expression and induces adhesion molecule expression in asthma.
abstract: Subjects with mild asthma underwent repeated low-dose allergen exposure and bronchial biopsies were examined for the expression of TNF-α and adhesion molecules. Bronchial biopsies from moderately severe asthmatics were then tested in an explant culture system to assess the effect of Der p and CDP-870, a TNF-α blocking pegylated-antibody Fab, on expression of TNF-α and adhesion molecules. Low-dose allergen challenge significantly upregulated sub-mucosal mast cells, TNF-α(+) cells, and VCAM. When bronchial explants were exposed to Der p and CDP 870 for 24h, CDP 870 caused a significant reduction in TNF-α release both at baseline and following stimulation with Der p allergen. The bronchial biopsies showed significant upregulation of TNF-α positive cells and ICAM-1 following exposure to Der p (p=0.03) and this was reduced in the presence of CDP-870. So, allergen exposure up-regulates TNF-α expression in asthma and down-stream targets, including adhesion molecules that contribute to airway inflammation.
authors: The Brooke Laboratories, Division of Infection, Inflammation, and Repair, University of Southampton School of Medicine, Southampton General Hospital, Southampton, SO16 6YD, UK. sureshbabu97@gmail.com
authors: Suresh K
authors: SK
authors: Babu
authors: Sarah M
authors: SM
authors: Puddicombe
authors: Hasan H
authors: HH
authors: Arshad
authors: Susan J
authors: SJ
authors: Wilson
authors: John
authors: J
authors: Ward
authors: Neil
authors: N
authors: Gozzard
authors: Gerry
authors: G
authors: Higgs
authors: Stephen T
authors: ST
authors: Holgate
authors: Donna E
authors: DE
authors: Davies
mesh_terms: D000328:Adult; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D012129:Respiratory Function Tests; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*; D055815:Young Adult
chemical_list: D039741:Antigens, Dermatophagoides; D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha