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https://hdl.handle.net/2440/9648
Type: | Journal article |
Title: | Paracrine upregulation of monocyte cyclooxygenase-2 by mediators produced by T lymphocytes: Role of interleukin 17 and interferon-γ |
Other Titles: | Paracrine upregulation of monocyte cyclooxygenase-2 by mediators produced by T lymphocytes: Role of interleukin 17 and interferon-gamma |
Author: | Stamp, L. James, M. Cleland, L. |
Citation: | Journal of Rheumatology, 2004; 31(7):1255-1264 |
Publisher: | J Rheumatol Publ Co |
Issue Date: | 2004 |
ISSN: | 0315-162X 1499-2752 |
Abstract: | <h4>Objective</h4>Cyclooxygenase (COX)-2 is an inducible eicosanoid-forming enzyme that is expressed at sites of inflammation. T lymphocytes and monocytes are found in close proximity at sites of inflammation, including synovitis. We investigated whether activated T lymphocytes express COX-2 and whether activated T cells upregulate monocyte COX-2 expression.<h4>Methods</h4>Human T lymphocytes and monocytes were isolated from fresh buffy coats by density gradient separation followed by passage through either nylon wool columns (T lymphocytes) or counter-current elutriation (monocytes). T lymphocytes were stimulated using anti-CD3 and anti-CD28 in a co-culture system with monocytes using transwells, which prevents cell-cell contact, but allows diffusion of soluble mediators.<h4>Results</h4>Repeated examination of COX isotypes in resting and stimulated T cells revealed COX-1, but not COX-2. Activated T cells produced a soluble mediator(s) that upregulated monocyte COX-2. Mediator production was inhibited by cyclosporin A. Activated T cells produced interleukin 17 (IL-17) and interferon-g (IFN-g), and in the co-culture IL-17-neutralizing antibodies partially reduced monocyte COX-2 expression, whereas IFN-g-neutralizing antibodies had the opposite effect. Exogenous IL-17 upregulated monocyte COX-2, although concentrations were high compared with those generated by stimulated T cells. By contrast, monocyte COX-2 expression was downregulated when monocytes were treated with IFN-g prior to stimulation with lipopolysaccharide.<h4>Conclusion</h4>Soluble mediators produced by activated T cells can influence induction of monocyte COX-2, with IL-17 acting as a positive paracrine regulator and IFN-g acting as a negative regulator. In rheumatoid joints, previously observed high concentrations of IL-17 and low concentrations of IFN-g could contribute to T cell-driven upregulation of monocyte COX-2. |
Keywords: | T-Lymphocytes Monocytes Cells, Cultured Humans Isoenzymes Eicosanoids Membrane Proteins Inflammation Mediators Interleukin-17 Lymphocyte Activation Paracrine Communication Up-Regulation Prostaglandin-Endoperoxide Synthases Cyclooxygenase 1 Cyclooxygenase 2 Interferon-gamma |
Appears in Collections: | Aurora harvest Medicine publications |
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