Therapeutic effects of combination using glucosamine plus tacrolimus (FK-506) on the development of atopic dermatitis-like skin lesions in NC/Nga mice.
Tacrolimus (FK-506) has been found to exhibit potent inhibitory effects on spontaneously developed dermatitis. We previously showed that glucosamine prevents the development of Atopic dermatitis (AD)-like skin lesions in NC/Nga mice. The aims of our study were to investigate the synergistic therapeutic efficacy of combination of glucosamine plus FK-506 in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 8 were used for treatment with glucosamine (500 mg/kg) alone, FK-506 (1.0 mg/kg) or in combination. The synergistic effects of combination therapy were evaluated by dermatitis scores, skin histology and immunological parameters such as IgE, Th2-mediated cytokines and chemokines, CD3(+) T cells and CLA(+) T cells. Combined therapy using glucosamine plus FK-506 improved the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores. The suppression of dermatitis by combined therapy was accompanied by a decrease in the plasma level of IgE and in the splenic level of IL-5, IL-13, TARC and eotaxin. Histological finding indicated that the dermal infiltration of inflammatory cells including mast cells and eosinophils was greatly reduced. Particularly, immunohistological evaluation reveals a reduction in CD3(+) T cells and CLA(+) cells in the combined therapy. Our findings suggest that combination therapy of glucosamine plus FK-506 was more synergistic efficacy than single-modality treatment with either alone to improve the development of established dermatitis in NC/Nga mice model. This combined immunosuppressive therapy may provide an effective therapeutic strategy for the treatment of AD.
Dongguk University Research Institute of Biotechnology, Medical Science Research Center, Goyang, Korea.
C-H
CH
Kim
K A
KA
Cheong
C D
CD
Park
A-Y
AY
Lee
D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis; D054413:Chemokine CCL11 / Q000096:biosynthesis; D054414:Chemokine CCL17 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D040001:Dermatophagoides farinae / Q000276:immunology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005944:Glucosamine / Q000494:pharmacology / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D018793:Interleukin-13 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D017252:CD3 Complex; C515457:Ccl11 protein, mouse; C499538:Ccl17 protein, mouse; D054413:Chemokine CCL11; D054414:Chemokine CCL17; D018925:Chemokines; D016207:Cytokines; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D015848:Interleukin-5; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D007073:Immunoglobulin E; D005944:Glucosamine; D016559:Tacrolimus