INVESTIGATIVE REPORT
19 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV
Topical Glucose Induces Claudin-1 and Filaggrin Expression in a Mouse Model of Atopic Dermatitis and in Keratinocyte Culture , Exerting Anti-inflammatory Effects by Repairing Skin Barrier Function
Kiyoko YAMADA 1 , 2 , Kenji MATSUSHITA 2 , 3 , Jingshu WANG 3 and Takuro KANEKURA 1
1
Department of Dermatology , 2 Department of Longevity Oral Science , Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , and 3 Department of Oral Disease Research , National Center for Geriatrics and Gerontology , Obu , Japan
Atopic dermatitis ( AD ) is a chronic inflammatory skin disease . Corticosteroids , which are widely used for AD treatment , have adverse effects , and alternative treatments are urgently needed . This study examined the effect of topical application of high-dose glucose on inflamed skin in a murine model of AD . High-dose glucose treatment on the ear reduced dermatitis scores and ear thicknesses in mite antigen-treated NC / Nga mice . The levels of thymus and activation-regulated chemokine ( TARC ), Th cytokines ( interleukin ( IL ) -4 , IL-5 , IL-12 , IL-13 , and ( interferon ) IFN-γ ), and IgE were decreased in the serum of high-dose glucose-treated mice . Expression of claudin-1 and filaggrin was reduced in the ear epithelium in the NC / Nga mice . However , the reduced expression was restored by topical treatment with high-dose glucose . High-dose glucose also induced the expression of claudin-1 and filaggrin in cultured human skin keratinocytes . Co-stimulation with IL-4 , IL-13 , and thymic stromal lymphoprotein downregulated the expression of filaggrin in culture . However , high-dose glucose treatment restored the reduced expression of filaggrin . These results suggest that high-dose glucose treatment suppresses inflammation in the skin lesions by improving the skin barrier function .
Key words : claudin-1 ; filaggrin ; sugar ; steroid ; anti-inflammation ; allergy reaction ; cytokines ; IgE ; skin barrier ; mouse model .
Accepted Oct 2 , 2017 ; Epub ahead of print Oct 2 , 2017 Acta Derm Venereol 2018 ; 98 : 19 – 25 .
Corr : Kenji Matsuhista , Department of Oral Disease Research , National Center of Geriatrics and Gerontology , 7-430 Morioka-machi , Obu , Aichi 747-8511 , Japan . E-mail : kmatsu30 @ ncgg . go . jp ; Takuro Kanekura , Department of Dermatology , Kagoshima University Graduate School of Medical and Dental Sciences , 8-35-1 Sakuragaoka , Kagoshima 890-8520 , Japan . E-mail : takurok @ m2 . kufm . kagoshima-u . ac . jp
Atopic dermatitis ( AD ) is a chronic inflammatory skin disease characterized by increased IgE in serum , pruritic and relapsing eczematous skin lesions with a thickened epidermis , skin barrier defects , and infiltration of inflammatory cells , such as lymphocytes , eosinophils and mast cells ( 1 – 3 ). Thymus and activation-regulated chemokine ( TARC ), interleukin ( IL ) -4, IL-5 , and IL-13 produced by Th2 cells are strongly associated with the onset and development of AD ( 4 , 5 ). Th2 cells are associated with the acute phase of AD . On the other hand , Th1 cells , which produce IL-12 and interferon ( IFN ) -γ , contribute to the pathogenesis of the chronic phase of AD ( 6 , 7 ). Corticosteroids have frequently been used for AD treatment ( 8 ). However , steroids have adverse effects in patients with AD ( 9 ) and alternative treatments are therefore needed .
Glucose is a major source of energy for mammalian cells . Abnormally high levels of glucose in the blood , as observed in diabetes , are harmful to the body and lead to the development of chronic complications , such as prolonged inflammation and impaired wound healing ( 10 – 13 ). However , topical application of sugars , such as honey and glycosaminoglycans , have wound-healing properties ( 14 , 15 ). Glucose , one of the main sugars in honey , promotes wound healing ( 16 – 19 ). However , little is known about the effect of topical application of glucose on skin inflammation .
Recent reports suggest that declining epidermal barrier function influences the pathological characteristics of AD . Filaggrin is expressed in the granular layers as a > 400 kDa precursor protein , profilaggrin . Profilaggrin is cleaved into filaggrin monomers and N- and C-terminal peptides at the boundary of the stratum corneum and stratum granulosum . Filaggrin monomers are further degraded into natural moisturizing factors that are thought to maintain hydration of the upper stratum corneum and reduce the pH of the skin surface ( 20 , 21 ). Filaggrin with both null mutations and loss-of-function variations is significantly associated with the development of AD in the European population ( 22 ). Tight junctions are also key contributors to the epidermal barrier , and claudin-1 , which is a main component of tight junctions in the epidermis , is crucial for transepidermal water loss ( TEWL ) and skin barrier function . Claudin-1 is decreased in skin lesions of patients with AD , triggering skin inflammation ( 23 ).
To determine how glucose improves skin inflammation , we examined the effect of topical application of high-dose glucose on the inflamed skin in a murine model of chronic AD . We focused on claudin-1 and filaggrin and examined the expression of these molecules after treatment with a high concentration of glucose in vitro and in vivo .
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2807 Acta Derm Venereol 2018 ; 98 : 19 – 25