n-3 Fatty acids inhibit transcription of human IL-13: implications for development of T helper type 2 immune responses

Abstract

Fish oil supplementation during pregnancy has been associated with lower levels of cord blood IL-13, suggesting that the administration of n-3 fatty acids may attenuate the development of allergic disease. The present study aimed to investigate the mechanism by which n-3 fatty acid administration influences the production of IL-13. Pregnant BALB/c mice were fed nutritionally complete high-fat diets (15 %, w/w) with an n-3 fatty acid-enriched (DHA 1 %, w/w) or control diet (0 % DHA) immediately following delivery. Pups were exposed during suckling and weaned to the maternal diet for the remainder of the study. The production of IL-13, IL-4, IL-10 and interferon-g from the splenocytes of ovalbumin (ova)-sensitised animals was assessed following in vitro ova stimulation or unstimulated conditions. Human T helper type 2 (Th2) cells were mitogen-stimulated in the presence or absence of DHA (10 mM) and assessed for IL-13 and IL-4 expression using intracellular flow cytometry. The influence on transcriptional activation was studied using a human IL-13 promoter reporter construct and electromobility shift assay. Ova-activated splenocytes from DHA-fed mice produced less IL-13 (57·2 (SE 21·7) pg/ml) and IL-4 (7·33 (SE 3·4) pg/ml) compared with cells from the animals fed the control diet (161·5 (SE 45·0), P, 0·05; 33·2 (SE 11·8), P, 0·05). In vitro, DHA inhibited the expression of IL-13 protein from human Th2 cells as well as transcriptional activation and binding of the transcription factors cyclic AMP response element binding and activating transcription factor 2 to the human IL-13 promoter. These data indicate the potential of n-3 fatty acids to attenuate IL-13 expression, and suggest that they may subsequently reduce allergic sensitisation and the development of allergic disease.

IL‐2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?

“…Peripheral blood mononuclear cells from healthy donors were obtained by density centrifugation using Ficoll Histopaque Plus (GE Healthcare, Chicago, IL). As previously described, helper T cells were isolated by negative selection with a CD4 + T cell Isolation Kit II (Miltenyi Biotech, San Diego, CA) and cultured in X‐Vivo 15 media (Lonza, Walkersville, MD) supplemented with 10% FBS (Wisent, Saint‐Jean‐Baptiste, QC, Canada), 1× penicillin‐streptomycin‐glutamine (Gibco, Invitrogen, Thermo Fisher Scientific, Waltham, MA). For Th2 differentiation, CD4 + T cells were activated for 3 days on plate‐bound antibody (α) against CD3 (clone UCHT1, 1 μg/mL) and αCD28 (clone 37407, 1 μg/mL) in the presence of recombinant human rhIL‐2 (5 ng/mL; R&D Systems Inc), rhIL‐4 (10–20 ng/mL; R&D Systems Inc), blocking antibody for interferonγ (IFNγ) (AF‐285‐NA, 1 µg/mL, R&D Systems Inc) and IL‐12 (Clone C8.6, 1 µg/mL, R&D Systems Inc).…”

The Toxicological Mechanisms of Environmental Soot (Black Carbon) and Carbon Black: Focus on Oxidative Stress and Inflammatory Pathways

“…A noble protein “NFAT” has also been reported as a key regulator of T-cell development and functions (278). A unique way of targeting T-cell activation can be the use of N3 fatty acids (omega-3 fatty acids), as they interrupts transcription of human IL-13, which indirectly inhibit the T-helper type 2 effecter immune responses (Figure 7) (279). More recently, the antagonism of noble microRNA-126 has been known to suppress the effecter functions of Th2 cells in the allergic airways disease (280).…”

ITCH Deficiency Protects From Diet-Induced Obesity

“…The appropriate dietary regimen to be administered during an anti-inflammatory metabolic treatment is also a relevant issue, since some forms of lipids are known to positively or negatively affect the inflammatory response (28,29). The effect of the inhibition of ITCH on adipose tissue might be additive to other pathways that have been demonstrated to be relevant to dampen metabolic inflammation in skeletal muscle, such as the TNF-a-converting enzyme pathway, which is positively restrained by pioglitazone, a PPAR-g agonist with anti-inflammatory effects, in patients with type 2 diabetes (30,31).…”