The Mannose Attenuates Murine Atopic Dermatitis-like Skin Lesions Through Down-regulation Of Thymic Stromal Lymphopoietin In Keratinocytes

Atopic dermatitis is a chronic,inflammatory disease,involving abnormal barrier function across multiple organ sites.The recurrent symptoms and unbearable itching place both mental and physical torture on the patient.At present most opinions are atopic dermatitis is a systemic disease that interacts with multiple factors including genetic factors,immune factors,and environmental factors.Studies have shown that barrier dysfunction exists in the epidermis of atopic dermatitis patients,and the skin at the lesion is in an inflammatory environment with an imbalance of Th2 and Thl.Activated Th2 cells drive the acute onset of the disease,while the Thl response maintains the chronic phase of atopic dermatitis.Th2 cytokines are usually expressed by Th2 lymphocytes,and play an important role in IgE-mediated rapid-type hypersensitivity and allergic diseases,meanwhile affect epidermal function and structural proteins which leading to barrier dysfunction.As we all know,tumor necrosis factor alpha(TNF-α)is a potent pro-inflammatory cytokine,which plays an important role in the regulation of the immune system.TNF-α is involved in vasodilation and edema formation,and promotes the adhesion of leukocytes to epithelium by stimulating the expression of adhesion molecules.It also regulates blood clotting during inflammation,promotes oxidative stress at the site of inflammation,and indirectly causes fever.At present,TNF-α has become a new target for clinical treatment,and anti-TNF-α therapy is quite effective for various inflammatory diseases.Patients with atopic dermatitis have significantly elevated levels of TNF-α in the skin lesions and serum,and TNF-α can be considered as a key regulator of AD inflammation.It is worth noting that external antigens cause a large expression of TNF-α in keratinocytes,which in turn cause autocrine as well as the expression of other inflammatory cytokines and chemokines such as IL-1β,IL-6,IL-8 and IL-33.In addition,TNF-α induces the secretion of TSLP by keratinocytes,which is an important substance in the pathogenesis of atopic dermatitis.Thymic stromal lymphocytopoietin(TSLP)is an epithelial-derived IL-7-like cytokine,which is essential for the induction and maintenance of Th2 type inflammation.It was found that the level of TSLP increased significantly in the skin lesions of AD patients,and it was more pronounced in acute AD than in chronic AD,suggesting that TSLP may plays a certain role in the pathogenesis of atopic dermatitis.Extensive research has shown that a large amount of thymic stromal lymphopoietin(TSLP)were released in keratinocytes,induced inflammation and eventually caused damage to the skin barrier,and can also stimulate neurons to trigger itching.Therefore,in this experiment,we mainly studied the inhibitory effect of mannose on the expression of thymic stromal lymphogenin in keratinocytes and its immunoregulatory effect in DNCB-induce atopic dermatitis in mice model.The ears and backs of C57 mice were treated with equal amount of high-concentration of DNCB and intermittent treatment with equal amount of low-concentration of DNCB to maintain and strengthen the atopic dermatitis model.Mice were randomly divided into the control group,DNCB group and DNCB+mannose group.A certain concentration of mannose was added to the drinking water of the mice in the DNCB+mannose group to allow the mice to drink freely.The mice in the control group and the DNCB group did not add mannose to the drinking water.All mice are fed the same diet and live in the same environment.It is conspicuous that the dermatitis symptoms of the backs in mice with mannose added to drinking water were less serious than that in the DNCB group,such as red spots,thickened epidermis,scales and scratches.Further tests showed that the pathological changes of inflammatory infiltration in DNCB+ mannose group were alleviated,and the levels of TSLP and TNF-α were decreased,accompanied by decreased expression of inflammatory cytokines.We further investigated the mechanism of mannose on the reduction of TSLP expression in atopic dermatitis lesions in vitro.In vitro experiments,mannoose reduced the phosphorylation of MAPK and NF-κb p65 as well as the expression of inflammatory cytokines in TNF-α stimulated Hacat cells.In brief,we demonstrated the role of mannose in regulating the expression levels of TSLP and inflammatory cytokines in atopic dermatitis,and mannose may be a new direction in the treatment of atopic dermatitis.