Pneumococcus activation of the 5-lipoxygenase pathway and production of glycoproteins in the middle ear of rats.
Pneumococcal otitis media is associated with the production of potent inflammatory mediators (leukotrienes), but the mechanism by which pneumococcus induces production of leukotrienes in the middle ear is poorly understood. In this study, up-regulation of 2 genes that govern the lipoxygenase pathway, cPLA2 and 5-LOX, was observed in rats following inoculation of pneumococcus into the middle ear cavity. Expression of cPLA2 was low, and 5-LOX gene expression was not detected in control animals. Up-regulation of cPLA2 and 5-LOX in middle ear epithelial cells was accompanied by an increase of high-molecular-weight glycoproteins in middle ear fluid and cells. These findings suggest that pneumococcus activates the lipoxygenase pathway by up-regulating expression of the cPLA2 and 5-LOX genes. This, in turn, may stimulate synthesis and secretion of high-molecular-weight glycoproteins that facilitate production of fluid in the middle ear cleft.
Lin
J
J
Otitis Media Research Center, Departments of Otolaryngology, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA. linxx004@maroon.tc.umn.edu
Vambutas
A
A
Haruta
A
A
Paparella
M M
MM
Giebink
G S
GS
Kim
Y
Y
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D004432:Ear, Middle / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis*; D009093:Mucus / Q000166:cytology / Q000201:enzymology; D010034:Otitis Media with Effusion / Q000378:metabolism*; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism; D011008:Pneumococcal Infections / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D015854:Up-Regulation
D006023:Glycoproteins; D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A