The lipid A of Burkholderia multivorans C1576 smooth-type lipopolysaccharide and its pro-inflammatory activity in a cystic fibrosis airways model.
Cystic fibrosis is an autosomal recessive disorder and it is characterised by chronic bacterial airway infection which leads to progressive lung deterioration, sometimes with fatal outcome. Burkholderia multivorans and Burkholderia cenocepacia are the species responsible for most of the infections of cystic fibrosis patients. Lipopolysaccharide endotoxins (LPSs) are among the foremost factors of pathogenesis of Gram-negative infection and, in particular, lipid A is the endotoxic portion of LPS responsible for eliciting host innate immune response. In this work, the complete primary structure of the lipid A from B. multivorans C1576 has been defined and, further, its pro-inflammatory activity in a cystic fibrosis airways model is shown. The structure of B. multivorans lipid A was attained by chemical, mass spectrometry and nuclear magnetic resonance analyses whereas its biological activity was assessed on the intestinal epithelial cell line CACO-2 cells, on the airway epithelial IB3-1 cells, carrying the ΔF508/W1282X CFTR mutation and on an ex vivo model of culture explants of nasal polyps.
Ieranò
Teresa
T
Dipartimento di Chimica Organica e Biochimica, Università degli Studi di Napoli Federico, Napoli, Italy.
Cescutti
Paola
P
Leone
Maria Rosaria
MR
Luciani
Alessandro
A
Rizzo
Roberto
R
Raia
Valeria
V
Lanzetta
Rosa
R
Parrilli
Michelangelo
M
Maiuri
Luigi
L
Silipo
Alba
A
Molinaro
Antonio
A
D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019117:Burkholderia / Q000737:chemistry*; D018938:Caco-2 Cells; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008050:Lipid A / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D009298:Nasal Polyps / Q000188:drug therapy; D021241:Spectrometry, Mass, Electrospray Ionization; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016209:Interleukin-8; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha