Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagenase was identified within naturally occurring rat chronic otitis media by the use of an immunohistochemical technique with peroxidase-antiperoxidase to stain the paraffin. Collagenase was found in fibroblasts, mononuclear cells, and osteoclast cells in the bone-resorbing area. Collagenase was found only in fibroblasts in contact with epithelial basal cells. Macrophages from rat peritoneum were cultured with different concentrations of a lipopolysaccharide. The prostaglandin E2 level reached a maximum during the 12- to 24-hour period in the presence of endotoxin. This prostaglandin E2 was confirmed by immunofluorescent staining. The endotoxin-activated macrophage produced an insignificant amount of collagenase. These findings suggest that activated macrophages may be able to stimulate fibroblast collagenase production through the chemical mediator prostaglandin E2. Also, the interaction between fibroblasts and epidermal cells appears to encourage and enhance the biochemical events resulting in bone resorption in chronic otitis media.
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PMID:Bone resorption factors in chronic otitis media. 608 44

The mechanisms that regulate mucin release in chronic otitis media with effusion, a leading cause of hearing loss in children, remain largely unknown. We developed an animal model using Sprague-Dawley rats to determine the factors responsible for mucin production in chronic otitis media with effusion. N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, was used to investigate the role of nitric oxide in mucin secretion by the middle ear epithelium. All rats underwent eustachian tube obstruction. In the first set of rats, the middle ear was then injected transtympanically with 35 microl of either 300 mOsm Krebs-Ringer bicarbonate buffer (control group) or 1 mg/ml lipopolysaccharide in Krebs-Ringer (experimental group 1). In a second set of rats, the middle ear space was injected with lipopolysaccharide and then infused at a continuous rate for 7 days with either Krebs-Ringer (experimental group 2) or 1 mmol/L L-NAME in Krebs-Ringer (experimental group 3) through an osmotic infusion pump. After 7 days the volume of effusion and the quantity of mucin collected were significantly greater in lipopolysaccharide-exposed ears than in controls. In addition, antimucin immunostaining demonstrated mucous cell hyperplasia in response to lipopolysaccharide. The lipopolysaccharide-induced production of mucin and mucous cell hyperplasia was inhibited in ears treated with lipopolysaccharide and L-NAME. These results suggest that nitric oxide is a mediator in the pathway of mucin secretion in chronic otitis media with effusion.
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PMID:Nitric oxide mediates mucin secretion in endotoxin-induced otitis media with effusion. 912 82

Pharmacological agents that can normalize or enhance the ciliary and mucociliary activity of the tubotympanum should also be able to break the vicious circle of chronic otitis media with effusion (OME). Roxythromycin (RXM) has been shown to enhance the ciliary activity in vitro and also stimulate the mucociliary activity in vivo and may therefore, when clinically applied, prevent not only occurrence but also recurrence of clinical OME. The present study was designed to discuss the possible preventive effect of RXM on endotoxin-induced OME in the guinea pig. A total of 120 guinea pigs were used. The normal control group was treated with intratympanic injection of 0.1 ml of physiologic saline solution. The saline-control group was treated with oral administration of physiologic saline solution for 14 successive days. The low-dosage group and the high-dosage group were treated with oral administration of 5 and 50 mg/kg of sairei-to for 14 successive days, respectively. Then, the saline-control group, the low-dosage group and the high-dosage group were treated with intratympanic injection of 0.1 ml of lipopolysaccharide solution (100 micrograms/ml) derived from Klebsiella pneumoniae. All 10 animals in the four groups were sacrificed 1, 3, and 7 days after the intratympanic injection, to examine ciliary activity, mucociliary clearance time, and mucosal pathology of the tubotympanum. The saline-control group exhibited middle ear effusions and pathologies similar to human OME. The incidence of middle ear effusions was significantly reduced in the low-dosage and high-dosage groups. Throughout the observation period, the ciliary activity in the tubotympanum was significantly reduced in the saline-control group as compared with that of the normal control group. By contrast, the ciliary activity in the low-dosage and high-dosage groups was not so reduced in the Eustachian tube and the middle ear close to the orifice. Mucociliary clearance time in the low-dosage and high-dosage groups was not different from that in the normal control group throughout the period. The tubotympanum in the saline-control group exhibited mucosal pathologies characteristic of OME in human. By contrast, the low-dosage and high-dosage groups exhibited much milder pathological changes in the tubotympanum than those in the saline-control group. In conclusion, clinical application of RXM could be an effective measure to prevent the occurrence of OME and also the recurrence of the disease, especially in OME-prone individuals.
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PMID:Roxythromycin prevents endotoxin-induced otitis media with effusion in the guinea pig. 934 86

Bacteria or their products may cause chronic inflammation and subsequent bone loss. This inflammation and bone loss may be associated with significant morbidity in chronic otitis media, periodontitis, endodontic lesions, and loosening of orthopedic implants caused by lipopolysaccharide (LPS)-contaminated implant particles. Currently, it is not clear how bacteria or endotoxin-induced bone resorption occurs and what cell types are involved. Here we report that Porphyromonas gingivalis, a periodontal pathogen, and Escherichia coli LPS induce osteoclastic cell formation from murine leukocytes in the absence of osteoblasts. In contrast, stimulation with parathyroid hormone had no effect. These multinucleated, tartrate-resistant acid phosphatase-positive cells were positive for receptor activator of NF-kappaB (RANK), the receptor for osteoprotegerin ligand (OPGL), also known as RANK ligand (RANKL). Blocking antibodies demonstrated that their formation was dependent upon expression of OPGL and, to a lesser extent, on tumor necrosis factor alpha. Mononuclear cells represented a significant source of OPGL production. In vivo, P. gingivalis injection stimulated OPGL expression in both mononuclear leukocytes and osteoblastic cells. Thus, these findings describe a pathway by which bacteria could enhance osteolysis independently of osteoblasts and suggest that the mix of cells that participate in inflammatory and physiologic bone resorption may be different. This may give insight into new targets of therapeutic intervention.
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PMID:Bacteria induce osteoclastogenesis via an osteoblast-independent pathway. 1201 Oct 8

Several middle ear (ME) pathologies are associated with ME gas deficit. These include in particular the chronic otitis media diseases that are associated with inflammation (hence, increased ME mucosal blood flow) and/or reduced Eustachian tube (ET) function. The present study models the trans-mucosal gas exchange in normal and inflamed middle ears of rats. The model evaluates the role of the gas diffusion path in the ME mucosa using mucosa thickness as its index and the role of the mucosal blood flow rate on ME gas economy in order to compare between normal and inflamed MEs. An experimental method employing ME gas volume changes at constant pressure due to trans-mucosal gas exchange, and blood gas values from the literature, was used in anaesthetized rats to corroborate the model. Mucosa thickness was measured as an index of the gas diffusion path between the ME space and the ME circulation. ME inner surface area was estimated from its measured gas volume. Inflammation was inflicted by applying lipopolysaccharide (LPS) into one ear. The contralateral ear served as control. ME gas volume decreased significantly faster with time (p=0.02) in inflamed ears (-0.107 microL min(-1) +/- 0.034 S.D., n=10) versus control ears (-0.067 microL min(-1) +/- 0.036 S.D., n=10). Mucosa thickness was significantly thicker in inflamed ears (48.4 microm +/- 11.0 S.D.) versus controls (20.5 microm +/- 10.1 S.D.). The mathematical model, the experimental results, and the blood gas values were used to estimate the relative effective mucosal blood flow rate. The model predicts that in spite of almost doubling mucosa thickness in LPS treated ears, the increased gas loss in inflamed ears may be explained by increased mucosal blood flow rate. We suggest that the ability to estimate ME blood flow as obtained by applying the model to the measurements, is relevant to medical management of inflamed ME.
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PMID:Middle ear gas loss in inflammatory conditions: the role of mucosa thickness and blood flow. 1678 Dec 3

Osteoclasts are the only cells capable of carrying out bone resorption and therefore are responsible for the osteolysis seen in infectious diseases such as chronic otitis media and infected cholesteatoma. Pseudomonas aeruginosa is the most common organism isolated from these infectious middle ear diseases. In this study, we examined the mechanisms by which P. aeruginosa lipopolysaccharide (LPS) stimulates osteoclastogenesis directly from mononuclear osteoclast precursor cells. Osteoclast precursors demonstrated robust, bone-resorbing osteoclast formation when stimulated by P. aeruginosa LPS only if previously primed with permissive, sub-osteoclastogenic doses of receptor activator of NF-kappaB ligand (RANKL), suggesting that LPS is osteoclastogenic only during a specific developmental window. Numerous LPS-elicited cytokines were found to be released by osteoclast precursors undergoing P. aeruginosa LPS-mediated osteoclast formation. Two lines of evidence suggest that several cytokines promote Oc formation in an autocrine/paracrine manner. First, inhibition of several cytokine pathways including TNF-alpha, IL-1, and IL-6 block the osteoclastogenesis induced by LPS. Secondly, increased expression of the receptors for TNF-alpha and IL-1 was demonstrated by real-time quantitative polymerase chain reaction. Such a mechanism has not previously been established and demonstrates the ability of osteoclast precursors to autonomously facilitate bone destruction.
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PMID:Lipopolysaccharide-induced osteoclastogenesis from mononuclear precursors: a mechanism for osteolysis in chronic otitis. 1914 62