Tumor necrosis factor-alpha-converting enzyme: its role in community-acquired pneumonia.
Bronchoalveolar lavage fluid recovered from infected and uninvolved lungs of patients with community-acquired pneumonia (CAP; n=16) on day 6+/-0.8 was analyzed for cytokine, soluble receptor, and antagonist levels. The role of tumor necrosis factor (TNF)-alpha-converting enzyme (TACE) in the resolution of the local inflammatory response was investigated. TNF-alpha, interleukin (IL)-1beta, and IL-6 were elevated in the infected versus uninvolved lobe, whereas IL-10 was not. Epithelial lining fluid (ELF) cytokine levels correlated with intracellular cytokine expression. Levels of proTNF-alpha were reciprocally related to TNF-alpha ELF levels. Levels of soluble receptors, generated by TACE cleavage of membrane-bound precursors, were compartmentalized to infected ELF. TACE was down-regulated by internalization in cells from the site of infection. These data demonstrate that, in vivo during CAP, TACE has a role in regulating resolution of the local inflammatory response by modulating levels of pro- and counterinflammatory mediators.
Greene
Catherine
C
Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. cmgreene@rcsi.ie
Lowe
Gregory
G
Taggart
Clifford
C
Gallagher
Paula
P
McElvaney
Noel
N
O'Neill
Shane
S
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D017714:Community-Acquired Infections / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D011014:Pneumonia / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000037:antagonists & inhibitors; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human