Tea pigments are oxidized products of polyphenols derived from tea leaves (Camellia sinensis). Theaflavins are constituents of tea pigments with antioxidant, antineoplastic and antiinflammatory properties similar to their parent compounds. The biological properties of polyphenols and theaflavins have been linked to their capacity to inhibit the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor, which is critically involved in the molecular regulation of a number of proinflammatory cytokines. The current study examines the requirement for NF-kappaB in the immunosuppressive effects mediated by tea antioxidants. Specifically, we tested the hypothesis that cytokines produced by type 1 (T(H1)) CD4(+) T cells which require NF-kappaB for gene expression, such as interleukin-2 (IL-2) and interferon gamma (IFN gamma), are selectively inhibited by tea pigments. We found that tea pigments potently suppress IL-2 secretion, IL-2 gene expression and the activation of NF-kappaB in murine spleens enriched for CD4(+) T cells, as expected. Consistent with our hypothesis, tea pigments also inhibited the induction of IFNgamma mRNA. However, the expression of the T(H2) cytokines IL-4 and IL-5, which lack functional NF-kappaB sites within their promoters was unexpectedly suppressed by tea pigments, as well. The results indicate that NF-kappaB may be only one of multiple transcription factors inhibited by tea pigments.

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The heart is one of a number of organs that may be affected in systemic lupus erythematosus (SLE), a prototypic autoimmune disease. Potential anatomical sites of involvement include the myocardium, pericardium, endocardium, valves, conduction system and blood vessels that subserve the heart. Typically, the severity of cardiovascular disease in lupus correlates with the degree of systemic inflammation, which is mirrored by the level of C-reactive protein (CRP) in the plasma. C-reactive protein, in turn is regulated by proinflammatory cytokines, such as interleukins (ILs) 1beta and 6. These cytokines have been found in functionally and/or structurally damaged areas of the heart and have been implicated in disease pathogenesis. It has been assumed that the source of these putatively pathogenetically relevant cytokines in the compromised heart is infiltrating mononuclear cells. This study tests the hypothesis that cardiomyocytes per se may contribute to proinflammatory cytokine production in the setting of systemic inflammation. Using as the experimental model MRL/MpJ-Tnfrs6(lpr) (MRL-lpr/lpr) mice, which spontaneously manifest an autoimmune syndrome that has clinical features of SLE, we show that ventricular homogenates and ventricular cardiomyocytes constitutively overexpress genes encoding the proinflammatory cytokines IL-1beta, IL-6, IL-10, and gamma interferon. The results suggest the possibility that proinflammatory cytokines emanating from the heart may actually contribute to the high levels of CRP that appear to aid in predicting subsequent cardiac events. Viewed in this setting, CRP becomes a footprint of an ongoing pathogenic process mediated, in part, by the heart muscle itself.

BackgoundPrevious studies have shown that the functional capacity of T cells may be modulated by the composition of fatty acids within, and the release of fatty acids from membrane phospholipids, particulary containing arachidonic acid (AA). The remodeling of AA within membrane phospholipids of resting and proliferating CD4+ and CD8+ T cells is examined in this study.ResultsSplenic T cells were cultured in the presence or absence of anti-CD3 mAb for 48 h then labeled with [3H]AA for 20 min. In unstimulated cells, labeled AA was preferentially incorporated into the phosphoglycerides, phosphatidylcholine (PC) followed by phosphatidylinositol (PI) and phosphatidylethanolamine (PE). During a subsequent chase in unlabeled medium unstimulated CD4+ and CD8+ T cells demonstrated a significant and highly selective transfer of free, labeled AA into the PC pool. In contrast, proliferating CD4+ and CD8+ T cells distributed labeled [3H]AA predominantly into PI followed by PC and PE. Following a chase in AA-free medium, a decline in the content of [3H]AA-PC was observed in association with a comparable increase in [3H]AA-PE. Subsequent studies revealed that the cold AA content of all PE species was increased in proliferating T cells compared with that in non-cycling cells, but that enrichment in AA was observed only in the ether lipid fractions. Finally, proliferating T cells preincubated with [3H]AA exhibited a significant loss of labeled arachidonate in the PC fraction and an equivalent gain in labeled AA in 1-alk-1'-enyl-2-arachidonoyl-PE during a chase in unlabeled medium.ConclusionThis apparent unidirectional transfer of AA from PC to ether-containing PE suggests the existence of a CoA-independent transacylase system in T cells and supports the hypothesis that arachidonoyl phospholipid remodeling may play a role in the regulation of cellular proliferation.