Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritis.
Vasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory neuropeptide with therapeutic potential demonstrated for collagen-induced arthritis. The aim of this study was to characterise its potential anti-arthritic effect on human monocytes, macrophages, T cells, and rheumatoid art...
| Hlavní autoři: | , , , , , , |
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| Médium: | Journal article |
| Jazyk: | English |
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BioMed Central
2003
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| _version_ | 1826291197506748416 |
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| author | Foey, A Field, S Ahmed, S Jain, A Feldmann, M Brennan, F Williams, R |
| author_facet | Foey, A Field, S Ahmed, S Jain, A Feldmann, M Brennan, F Williams, R |
| author_sort | Foey, A |
| collection | OXFORD |
| description | Vasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory neuropeptide with therapeutic potential demonstrated for collagen-induced arthritis. The aim of this study was to characterise its potential anti-arthritic effect on human monocytes, macrophages, T cells, and rheumatoid arthritis synovial membrane cells. Monocytes, macrophages, and T cells derived from human peripheral blood were treated with VIP and compared with other cAMP-elevating drugs for a range of activating stimuli. Cytokine production was assessed for cell cultures and, in addition, the ability of VIPs to activate cAMP response element binding protein. VIP partially suppressed monocyte- and macrophage-derived tumour necrosis factor alpha (TNF-alpha) with no effect on IL-10, whereas VIP fails to regulate IL-10 and TNF-alpha production by T lymphocytes. No such modulation of cytokine profile was observed for rheumatoid arthritis synovial membrane cells. Elevation of intracellular cAMP, on the other hand, potently suppressed macrophage TNF-alpha production and modulated T-cell response by inhibiting TNF-alpha and IFN-gamma. VIP's lack of effect on IL-10 and its slight effect on TNF-alpha results from cAMP being rapidly degraded as the phosphodiesterase IV inhibitor, rolipram, rescues cAMP-dependent activation of cAMP response element binding protein. Interestingly, macrophages stimulated with phorbol 12-myristate 13-acetate/ionomycin displayed an augmented IL-10 response upon addition of dibutyryl cAMP, with corresponding downregulation in TNF-alpha, suggesting a complex interaction between protein kinase C and protein kinase A in cytokine regulation. In conclusion, VIP may represent an efficaceous anti-arthritic treatment modulating macrophage and T-cell cytokine profiles when used alongside a phosphodiesterase inhibitor. |
| first_indexed | 2024-03-07T02:55:48Z |
| format | Journal article |
| id | oxford-uuid:af3ef70c-d506-4130-b6e5-16efcb7d6a6a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:55:48Z |
| publishDate | 2003 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:af3ef70c-d506-4130-b6e5-16efcb7d6a6a2022-03-27T03:48:19ZImpact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:af3ef70c-d506-4130-b6e5-16efcb7d6a6aEnglishSymplectic Elements at OxfordBioMed Central2003Foey, AField, SAhmed, SJain, AFeldmann, MBrennan, FWilliams, RVasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory neuropeptide with therapeutic potential demonstrated for collagen-induced arthritis. The aim of this study was to characterise its potential anti-arthritic effect on human monocytes, macrophages, T cells, and rheumatoid arthritis synovial membrane cells. Monocytes, macrophages, and T cells derived from human peripheral blood were treated with VIP and compared with other cAMP-elevating drugs for a range of activating stimuli. Cytokine production was assessed for cell cultures and, in addition, the ability of VIPs to activate cAMP response element binding protein. VIP partially suppressed monocyte- and macrophage-derived tumour necrosis factor alpha (TNF-alpha) with no effect on IL-10, whereas VIP fails to regulate IL-10 and TNF-alpha production by T lymphocytes. No such modulation of cytokine profile was observed for rheumatoid arthritis synovial membrane cells. Elevation of intracellular cAMP, on the other hand, potently suppressed macrophage TNF-alpha production and modulated T-cell response by inhibiting TNF-alpha and IFN-gamma. VIP's lack of effect on IL-10 and its slight effect on TNF-alpha results from cAMP being rapidly degraded as the phosphodiesterase IV inhibitor, rolipram, rescues cAMP-dependent activation of cAMP response element binding protein. Interestingly, macrophages stimulated with phorbol 12-myristate 13-acetate/ionomycin displayed an augmented IL-10 response upon addition of dibutyryl cAMP, with corresponding downregulation in TNF-alpha, suggesting a complex interaction between protein kinase C and protein kinase A in cytokine regulation. In conclusion, VIP may represent an efficaceous anti-arthritic treatment modulating macrophage and T-cell cytokine profiles when used alongside a phosphodiesterase inhibitor. |
| spellingShingle | Foey, A Field, S Ahmed, S Jain, A Feldmann, M Brennan, F Williams, R Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritis. |
| title | Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritis. |
| title_full | Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritis. |
| title_fullStr | Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritis. |
| title_full_unstemmed | Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritis. |
| title_short | Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritis. |
| title_sort | impact of vip and camp on the regulation of tnf alpha and il 10 production implications for rheumatoid arthritis |
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