Research Article
Conjugated linoleic acid attenuates 2,4-dinitrofluorobenzene-induced atopic dermatitis in mice through dual inhibition of COX-2/5-LOX and TLR4/NF-κB signaling

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Abstract

Conjugated linoleic acid (CLA), commonly found in beef, lamb and dairy products, has been reported to exhibit anti-inflammatory and antipruritus effects and to inhibit the release of chemical mediators such as histamine and eicosanoid in laboratory rodents. The chief objective of the study is to assess the efficacy of CLA on atopic dermatitis (AD) in mice and to explore possible mechanisms with CLA treatments. To develop a new therapy for AD, the anti-AD potential of CLA was investigated by inducing AD-like skin lesions in mice using 2,4-dinitrofluorobenzene. We evaluated dermatitis severity; histopathological changes; serum levels of T helper (Th) cytokines (interferon-γ, interleukin-4); changes in protein expression by western blotting and immunohistochemistry staining for cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), toll like receptor 4 (TLR-4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB) and tumor necrosis factor α (TNF-α); and production of the proinflammatory lipid mediators, such as prostaglandin E2 and leukotriene B4, in the skin lesions. Treatment with CLA ameliorated the development of AD-like clinical symptoms and effectively inhibited epidermal hyperplasia and infiltration of mast cells and CD4+ T cells in the AD mouse skin. Total serum immunoglobulin E levels and the expression levels of Th1/Th2 cytokines and lipid mediators in dorsal skin were dramatically suppressed by CLA. Furthermore, CLA down-regulated the expressions of COX-2, 5-LOX, TLR4, MyD88, NF-κB and TNF-α. Taken together, our findings demonstrate the potential usefulness of CLA as an anti-inflammatory dietary supplement or drug for the prevention and management of AD skin diseases by modulating the COX-2/5-LOX and TLR4/MyD88/NF-κB signaling pathways.

Section snippets

Chemicals and reagents

DNFB (purity 99%) was purchased from Alfa Aesar (Heysham, UK). Olive oil was obtained from Aladdin (Shanghai, China). DEX (purity 98%) was supplied by Saen Chemical Technology Co. Ltd. (Shanghai, China). CLA (containing 50:50 mixture of cis-9, trans-11 and trans-10, cis-12 CLA isomers) was obtained from Qingdao Auhai Biotech Co., Ltd. (Shangdong, China). Enzyme-linked immunosorbent assay (ELISA) kits were produced by Bioswamp Life Science Lab. (Wuhan, China). CD4, cyclooxygenase-2 (COX-2),

CLA alleviates DNFB-induced AD-like symptoms

Fig. 1C indicates that repeated application of DNFB to mouse dorsal skin induced clinical characteristics of AD, such as dryness, erythema, erosion, edema/excoriation and scaling on the final day of the experiment. Co-treatment of CLA ameliorated these phenotypes in skin lesions, with most of the mice exhibiting slightly scarred or dry skin. Meanwhile, the development of skin lesions was inhibited by oral application of CLA (Fig. 2A). On day 29, CLA markedly decreased DNFB-induced increases in

Discussion

AD is one of the most common relapsing inflammatory skin diseases prevailing around the world, which is characterized by Th1/Th2 imbalance, IgE hypersensitivity and typical clinical signs of chronic pruritus and eczematous skin lesions [2,39]. Whigham et al. [17] proved that CLA was able to reduce antigen-induced histamine and PGE2 release from tracheas of guinea pigs sensitized to chicken egg ovalbumin, suggesting the potential therapeutic effect of CLA on AD. To place the results of the

Conflicts of interest

The authors declare no conflict of interest.

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