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)

The pneumonic lesions and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS; Ovis canadensis) are more severe than those in the related species, domestic sheep (DS; Ovis aries), under both natural and experimental conditions. Leukotoxin (Lkt) and lipopolysaccharide (LPS) are the most important virulence factors of this organism. One hallmark of pathogenesis of pneumonia is the influx of polymorphonuclear leukocytes (PMNs) into the lungs. Lkt-induced cytolysis of PMNs results in the release of cytotoxic compounds capable of damaging lung tissue. Interleukin-8 (IL-8) is a potent PMN chemoattractant. The objective of the present study was to determine if there is differential expression of IL-8 by the macrophages and PMNs of BHS and DS in response to M. haemolytica. Macrophages and PMNs of BHS and DS were stimulated with heat-killed M. haemolytica or LPS. IL-8 expression by the cells was measured by enzyme-linked immunosorbent assays and real-time reverse transcription-PCR (RT-PCR). The PMNs of BHS expressed severalfold higher levels of IL-8 than those of DS upon stimulation. Lesional lung tissue of M. haemolytica-infected BHS contained significantly higher levels of IL-8 than nonlesional tissue. The bronchoalveolar lavage (BAL) fluid of infected BHS also contained higher levels of IL-8 than that of infected DS. Depletion of IL-8 reduced migration of PMNs toward BAL fluid by approximately 50%, indicating that IL-8 is integral to PMN recruitment to the lung during M. haemolytica infection. Excessive production of IL-8, enhanced recruitment of PMNs, and PMN lysis by Lkt are likely responsible for the severity of the lung lesions in M. haemolytica-infected BHS.
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PMID:Differential expression of interleukin-8 by polymorphonuclear leukocytes of two closely related species, Ovis canadensis and Ovis aries, in response to Mannheimia haemolytica infection. 2051 32

Ulcerative colitis involves complicated etiology and presents diverse symptoms including intestine inflammation, bowel pain and diarrhea. Anti-inflammatory drugs are the mainstay in patient care, accompanied with antidiarrhea and analgesic agents used as symptomatic treatment. A classic traditional Chinese medicine formula, Fructus Mume pill (FMP), showed remarkable therapeutic efficacy in treating ulcerative colitis. However, since it contains many herbs and countless chemicals, the underlying mechanism is not clear. In this study, we selected three alkaloids from FMP, namely, berberine, hypaconitine and skimmianine to study the individual drug effect and compare these results with the BHS combination on: 1) The recovery of ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. 2) Mice with xylene-induced acute exudative edema and acetic acid-induced writhing. 3) Gastrointestinal transit inhibition, and 4) the response of HT29 cells after treatment with lipopolysaccharide. We found that the compound hypaconitine showed a potent analgesic effect, while skimmianine acted as an antidiarrhea agent and the component berberine was the key agent exerting anti-inflammatory effect. However, since berberine killed the commensal bacteria and induced lipopolysaccharide release, it could at the same time aggravate colon inflammation. The three-alkaloid combination BHS produced complementary and synergistic effects in colon inflammation recovery, relieving acetic acid-induced bowel pain and xylene-induced acute exudative edema. BHS also decreased lipopolysaccharide production and enhanced the therapeutic efficacy. It is hoped that this study will lay the foundation to further dissect and understand the FMP formula to improve the treatment with simplified and well defined drug combinations for this dreadful disease.
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PMID:Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconitine and skimmianine on the ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. 2096 48