Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-10-21
pubmed:abstractText
Buruli ulcer is a chronic and progressive necrotizing ulcer for which there is no medical treatment. Historically, a soluble toxin (factor) derived from the causative Mycobacterium ulcerans was found to induce the massive necrosis of skin and s.c. tissue seen in this condition. However, the persistence of the disease is thought to be caused by a lack of any immune response. We therefore investigated whether the factor was related to immunosuppression. A protocol to partially purify the factor was developed, and its effects on immune competent cells were tested. The factor produced >95% inhibition of LPS-induced release of TNF and IL-10 from human monocytes and caused a loss of adherence of these cells without cell death. The factor also blocked the production of IL-2 from activated T lymphocytes. The factor had no effect on TNF-induced cytotoxicity, but abrogated TNF-induced NF-kappa B activation. Surprisingly, a synergy was observed between the factor and phorbol ester-directed NF-kappa B activation. The factor had no effect on IL-1- or LPS-induced NF-kappa B activity, indicating selective activity of the factor. The factor did not inhibit the degradation of I kappa B alpha induced by TNF, indicating that the target for its activity lies within an undefined part of the TNF signaling mechanism. The data indicate that the localized immunosuppression associated with Buruli ulcer relates to the activity of the released factor, and this may provide a target for future therapeutic strategies for this intractable disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3928-35
pubmed:dateRevised
2010-8-25
pubmed:meshHeading
pubmed-meshheading:10490994-Animals, pubmed-meshheading:10490994-Apoptosis, pubmed-meshheading:10490994-Bacterial Toxins, pubmed-meshheading:10490994-Cytokines, pubmed-meshheading:10490994-Exotoxins, pubmed-meshheading:10490994-Guinea Pigs, pubmed-meshheading:10490994-Humans, pubmed-meshheading:10490994-Immunity, Innate, pubmed-meshheading:10490994-Immunosuppressive Agents, pubmed-meshheading:10490994-Interleukin-10, pubmed-meshheading:10490994-L Cells (Cell Line), pubmed-meshheading:10490994-Lipids, pubmed-meshheading:10490994-Mice, pubmed-meshheading:10490994-Monocytes, pubmed-meshheading:10490994-Mycobacterium ulcerans, pubmed-meshheading:10490994-NF-kappa B, pubmed-meshheading:10490994-Solubility, pubmed-meshheading:10490994-T-Lymphocytes, pubmed-meshheading:10490994-Tumor Cells, Cultured, pubmed-meshheading:10490994-Tumor Necrosis Factor-alpha
pubmed:year
1999
pubmed:articleTitle
The inhibitory action of Mycobacterium ulcerans soluble factor on monocyte/T cell cytokine production and NF-kappa B function.
pubmed:affiliation
Infectious Diseases and Microbiology, Imperial College, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't