Impact of cAMP on the T-cell response to type II collagen.
There is considerable interest in the possible use of cAMP-elevating agents in the treatment of autoimmune diseases such as rheumatoid arthritis. The objective of this study was to evaluate the impact of different cAMP-elevating agents on the T-cell response to type II collagen within the context of...
| Główni autorzy: | , , , |
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| Format: | Journal article |
| Język: | English |
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2004
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| _version_ | 1826283239035109376 |
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| author | Ozegbe, P Foey, A Ahmed, S Williams, R |
| author_facet | Ozegbe, P Foey, A Ahmed, S Williams, R |
| author_sort | Ozegbe, P |
| collection | OXFORD |
| description | There is considerable interest in the possible use of cAMP-elevating agents in the treatment of autoimmune diseases such as rheumatoid arthritis. The objective of this study was to evaluate the impact of different cAMP-elevating agents on the T-cell response to type II collagen within the context of collagen-induced arthritis, a murine model of rheumatoid arthritis. Spleen cells or lymph node cells from type-II-collagen-immunized DBA/1 mice were cultured in the presence of type II collagen plus one of five different cAMP-elevating agents: rolipram, forskolin, prostaglandin E2, 8-bromo-cAMP, or cholera toxin. Levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-5 were measured in culture supernatants by enzyme-linked immunosorbent assay. All of the cAMP-elevating agents tested were found to profoundly suppress IFN-gamma production in a dose-dependent manner. IL-4 and IL-5 production was slightly up-regulated at low concentrations of the cAMP-elevating agents and was modestly suppressed at the highest concentrations of cAMP-elevating agents. Experiments were then carried out to determine whether T cells were directly affected by cAMP-elevating agents or whether the immunomodulatory effects were mediated via antigen-presenting cells. Pulsing T cells alone for a brief period with cholera toxin produced an almost identical effect to pulsing antigen-presenting cells alone, i.e. down-regulation of proliferation, down-regulation of IFN-gamma production with little effect on IL-5 production. It was concluded that cAMP-elevating agents suppressed T helper type 1 responses to type II collagen to a greater extent than T helper type 2 responses. The cAMP-elevating agents could directly influence the activity of T cells but, in addition, influenced the ability of antigen-presenting cells to support T helper type 1 responses. |
| first_indexed | 2024-03-07T00:55:55Z |
| format | Journal article |
| id | oxford-uuid:8812c920-b4c8-46db-af8e-2c64ad1e532f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:55:55Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:8812c920-b4c8-46db-af8e-2c64ad1e532f2022-03-26T22:14:37ZImpact of cAMP on the T-cell response to type II collagen.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8812c920-b4c8-46db-af8e-2c64ad1e532fEnglishSymplectic Elements at Oxford2004Ozegbe, PFoey, AAhmed, SWilliams, RThere is considerable interest in the possible use of cAMP-elevating agents in the treatment of autoimmune diseases such as rheumatoid arthritis. The objective of this study was to evaluate the impact of different cAMP-elevating agents on the T-cell response to type II collagen within the context of collagen-induced arthritis, a murine model of rheumatoid arthritis. Spleen cells or lymph node cells from type-II-collagen-immunized DBA/1 mice were cultured in the presence of type II collagen plus one of five different cAMP-elevating agents: rolipram, forskolin, prostaglandin E2, 8-bromo-cAMP, or cholera toxin. Levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-5 were measured in culture supernatants by enzyme-linked immunosorbent assay. All of the cAMP-elevating agents tested were found to profoundly suppress IFN-gamma production in a dose-dependent manner. IL-4 and IL-5 production was slightly up-regulated at low concentrations of the cAMP-elevating agents and was modestly suppressed at the highest concentrations of cAMP-elevating agents. Experiments were then carried out to determine whether T cells were directly affected by cAMP-elevating agents or whether the immunomodulatory effects were mediated via antigen-presenting cells. Pulsing T cells alone for a brief period with cholera toxin produced an almost identical effect to pulsing antigen-presenting cells alone, i.e. down-regulation of proliferation, down-regulation of IFN-gamma production with little effect on IL-5 production. It was concluded that cAMP-elevating agents suppressed T helper type 1 responses to type II collagen to a greater extent than T helper type 2 responses. The cAMP-elevating agents could directly influence the activity of T cells but, in addition, influenced the ability of antigen-presenting cells to support T helper type 1 responses. |
| spellingShingle | Ozegbe, P Foey, A Ahmed, S Williams, R Impact of cAMP on the T-cell response to type II collagen. |
| title | Impact of cAMP on the T-cell response to type II collagen. |
| title_full | Impact of cAMP on the T-cell response to type II collagen. |
| title_fullStr | Impact of cAMP on the T-cell response to type II collagen. |
| title_full_unstemmed | Impact of cAMP on the T-cell response to type II collagen. |
| title_short | Impact of cAMP on the T-cell response to type II collagen. |
| title_sort | impact of camp on the t cell response to type ii collagen |
| work_keys_str_mv | AT ozegbep impactofcamponthetcellresponsetotypeiicollagen AT foeya impactofcamponthetcellresponsetotypeiicollagen AT ahmeds impactofcamponthetcellresponsetotypeiicollagen AT williamsr impactofcamponthetcellresponsetotypeiicollagen |