The immunomodulatory effects of novel beta-oxa, beta-thia, and gamma-thia polyunsaturated fatty acids on human T lymphocyte proliferation, cytokine production, and activation of protein kinase C and MAPKS

Costabile, M., Hii, C. S. T., Melino, M., Easton, C. and Ferrante, A. (2005) The immunomodulatory effects of novel beta-oxa, beta-thia, and gamma-thia polyunsaturated fatty acids on human T lymphocyte proliferation, cytokine production, and activation of protein kinase C and MAPKS. Journal of Immunology, 174 1: 233-243.

Author Costabile, M.
Hii, C. S. T.
Melino, M.
Easton, C.
Ferrante, A.
Title The immunomodulatory effects of novel beta-oxa, beta-thia, and gamma-thia polyunsaturated fatty acids on human T lymphocyte proliferation, cytokine production, and activation of protein kinase C and MAPKS
Formatted title
The immunomodulatory effects of novel β-oxa, β-thia, and γ-thia polyunsaturated fatty acids on human T lymphocyte proliferation, cytokine production, and activation of protein kinase C and MAPKs
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2005-01
Sub-type Article (original research)
Volume 174
Issue 1
Start page 233
End page 243
Total pages 11
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Abstract We have recently demonstrated that a novel n-3 long chain polyunsaturated fatty acid (PUFA) (β-oxa 21:3n-3) was a more potent and more selective anti-inflammatory agent than n-3 PUFA. To gain further insights into this technology, we synthesized other novel PUFA consisting of β-oxa, β-thia, and γ-thia compounds. All three types displayed anti-inflammatory activity. Each of the unsaturated β-oxa fatty acids showed similar inhibition of PHA-PMA-induced T cell proliferation with a parallel inhibition of TNF-β production. However, β-oxa 25:6n-3 and β-oxa 21:4n-3 displayed lower inhibitory action on IFN-γ production. Surprisingly, β-oxa 23:4n-6 and β-oxa 21:3n-6 had marginal effect on IL-2 production. Thus, structural variation can generate selectivity for different immunological parameters. The β-thia compounds 23:4n-6, 21:3n-6, and 21:3n-3 were highly effective in inhibiting all immunological responses. Of the two γ-thia PUFA tested, γ-thia 24:4n-6 was a strong inhibitor of all responses apart from IL-2, but γ-thia 22:3n-6 had very little inhibitory effect. Two of the most active compounds, β-thia 23:4n-6 and β-thia 21:3n-6, were studied in more detail and shown to have an IC 50 of 1-2 μM under optimal conditions. Thus, these PUFA retain the immunosuppressive properties of the n-3 PUFAs, 20:5n-3 and 22:6n-3, but not the neutrophil-stimulating properties. Their action on T lymphocytes is independent of cyclooxygenase or lipoxygenase activity, and they act at a postreceptor-binding level by inhibiting the activation of protein kinase C and ERK1/ERK2 kinases.
Keyword DIETARY SUPPLEMENTATION
SUPEROXIDE PRODUCTION
HUMAN NEUTROPHILS
CELL-ACTIVATION
IN-VITRO
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 09 Mar 2011, 08:49:01 EST