Uddin, J., Gonzalez, A.E., Gilman, R.H. et al. (6 more authors) (2006) Neurocysticercal antigens stimulate chemokine secretion from human monocytes via an NF-κB-dependent pathway. Microbes and Infection, 8 (7). pp. 1732-1740. ISSN 1286-4579
Abstract
Neurocysticercosis, infection with larval Taenia solium, is a common, serious neuroparasitic infection. Larval degeneration results in inflammatory cell influx and granuloma formation which leads to clinical symptomatology. The role of chemokines in such cell influx is unknown. We demonstrate that monocyte stimulation by T. solium larval antigen (TsAg) results in a differential profile of CXCL8/IL-8 (146.5 ± 8.5 ng/ml after 24 h), CCL2/MCP-1 (267 ± 4 ng/ml after 48 h) and CCL3/MIP-1α (1.72 ± 0.43 ng/ml after 8 h) secretion. There was coordinate mRNA accumulation reaching maximum at 1 h for CCL3 and 2 h for CXCL8 and CCL2. TsAg induced maximal nuclear binding of p65, p50 and c-rel subunits of the transcriptional regulator NF-κB by 2 h. IκBα but not IκBβ was degraded within 10 min before resynthesis by 2 h. Pre-treatment with the broad-spectrum NF-κB inhibitor pyrrolidine dithiocarbamate caused complete abrogation of TsAg-induced CCL2 secretion (p = 0.005) and 91% reduction of CXCL8 secretion (p = 0.0003). TsAg was unable to induce CXCL8 promoter activity in Toll-like receptor (TLR)-2 or TLR-4/MD-2 transfected HeLa cells in the absence of lectins or other adaptor molecules. In summary, our data demonstrate that TsAg induces chemokine secretion via specific pathways dependent on NF-κB but not TLR-4/TLR-2, and indicate a potential mechanism whereby larval degeneration results in brain inflammation.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2006 Elsevier SAS. |
Keywords: | Animals; Antigens, Helminth; Cell Nucleus; Cells, Cultured; Chemokine CCL2; Chemokines; Chemokines, CXC; Cysticercus; Gene Expression; Humans; I-kappa B Proteins; Interleukin-8; Monocytes; NF-KappaB Inhibitor alpha; NF-kappa B; NF-kappa B p50 Subunit; Pyrrolidines; RNA, Messenger; Swine; Thiocarbamates; Toll-Like Receptors; Transcription Factor RelA |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Dec 2024 09:47 |
Last Modified: | 13 Dec 2024 09:49 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.micinf.2006.02.009 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:220804 |