Mucin hypersecretion in the airways is a hallmark of Chronic Obstructive Pulmonary Diseases (COPD) and in particular of chronic bronchitis. This study investigates how bacterial products such as LPS affect mucin production (the main constituent of mucus) and how surfactant phospholipids may modulate this effect. In two human bronchoepithelial cell lines, NCI-H292 and Calu-3, both of which express mucin gene and secrete mucins, LPS treatment resulted in an increase in secretion, production and of gene expression of MUC5AC, one of the main mucins present in airways secretion, and of MUCI, a membrane anchored mucin. LPS treatment also increased the presence of fucose, sialic acid and N-acetylgalactosamine, the main elements involved in mucin glycosylation. Using fluorescent microscopy, TLR4, part of the complex receptor for LPS, was detected on the surface of these cells and CD74, a co receptor for LPS, detected internally. Following LPS exposure, CD14 was released from cells and was detected colocalised with TLR4. LPS induced NFкB activity and the utilisation of a NFкB inhibitor abolished the effect of LPS on mucin gene expression. The main surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPC), inhibited the effect of LPS on mucin production and glycosylations. It reduced NFкB activity induced by LPS but had no effect on CD14 release. It also inhibited mucin gene expression induced by IL-lβ and by TNF-α. Other surfactant phospholipids were tested: palmitoyl-linoleoyl-phosphatidylcholine (PLPC) had a similar modulatory effect to that seen with DPPC, palmitoyl-arachidonoylphosphatidylcholine (PAPC) showed no effect whereas palmitoyl-oxovaleroylphosphorylcholine (POVPC), a product of oxidised PAPC, also inhibited the activity of LPS. These results suggest that bacterial products in the airways are capable of inducing mucin secretion and that surfactant phospholipids modulate this effect. These findings indicate a therapeutic role for surfactant supplementation in chronic respiratory diseases.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:629878 |
| Date | January 2005 |
| Creators | Caillon, Fabienne |
| Contributors | Jones, K. P.; Jackson, S. K. |
| Publisher | Cardiff Metropolitan University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/10369/6445 |
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