Ann Dermatol.  2015 Apr;27(2):121-127. 10.5021/ad.2015.27.2.121.

Retinoic Acid Promotes Interleukin-4 Plasmid-Dimethylsulfoxide Topical Transdermal Delivery for Treatment of Psoriasis

• Chen ZW
• Zhang YB
• Chen XJ
• Liu X
• Wang Z
• Zhou XK
• Qiu J
• Zhang NN
• Teng X
• Mao YQ
• Liu CY
• Wei YQ
• Li J

• KMID: 2264799
• DOI: http://doi.org/10.5021/ad.2015.27.2.121

Abstract

BACKGROUND
Psoriasis is an autoimmune disease that is caused by a shift in the Th1/Th2 balance toward Th1-dominant immunity. It has been established as an effective treatment to counteract psoriasis by subcutaneous injection of recombinant interleukin (IL)-4, and IL-4 gene therapy by topical transdermal penetration has shown its antipsoriatic effect in mice. Retinoic acid (RA) and dimethylsulfoxide can increase the efficiency of gene transfection in the topical transdermal delivery system.
OBJECTIVE
We investigated whether RA could improve anti-psoriasis efficiency using IL-4 expression plasmid pORF-mIL-4 (pIL-4) via transdermal delivery system in K14-vascular endothelial growth (K14-VEGF) factor transgenic mice.
METHODS
After pretreatment with RA, plasmid pIL-4 in 10% dimethylsulfoxide was applied to the ear skin by topical transdermal penetration. Hematoxylin- eosin staining and immunohistochemistry were performed with ear samples to evaluate anti-psoriasis efficiency in mice.
RESULTS
The psoriasis pathological features were relieved and psoriasis-associated factors were significantly reduced.
CONCLUSION
Our results reveal that topical application of pIL-4 in dimethylsulfoxide by transdermal delivery with RA pretreatment can improve psoriasis significantly.

Keyword

Dimethyl sulfoxide; Gene therapy; Interleukin-4; Psoriasis; Retinoic acid; Transdermal

MeSH Terms

Animals
Autoimmune Diseases
Dimethyl Sulfoxide
Ear
Eosine Yellowish-(YS)
Genetic Therapy
Immunohistochemistry
Injections, Subcutaneous
Interleukin-4*
Interleukins
Mice
Mice, Transgenic
Plasmids
Psoriasis*
Skin
Transfection
Tretinoin*
Dimethyl Sulfoxide
Eosine Yellowish-(YS)
Interleukin-4
Interleukins
Tretinoin

Figure

• 

  Fig. 1 Histological phenotype improvement of the ear after administration in a pharmacodynamic experiment. (A1~A5) Macroscopic characteristics of the ears. Images show macroscopic findings of the mice after treatment with A1: RA+DMSO+IL-4; A2: DMSO+IL-4; A3: RA+DMSO+MCS; A4: DMSO+MCS; A5: saline. (B1~B5) Pathological characteristics of the ears. Images show H&E staining of the ears after treatment with B1: RA+DMSO+IL-4; B2: DMSO+IL-4; B3: RA+DMSO+ MCS; B4: DMSO+MCS; B5: saline (original magnification ×200). Thickness A refers to the epidermis thickness of the other four groups; thickness B was the epidermis thickness of RA+DMSO+pIL-4. Vertical ordinate was the ratio of other group to RA+DMSO+pIL-4. For the rectangle, the top and bottom respectively means the epidermal thickness ratio of the maximum to the minimum. Thick solid lines mean the mean value. Thickness A: RA+DMSO+IL-4; DMSO+IL-4; RA+DMSO+ MCS; DMSO+MCS; and saline. Thickness B: RA+DMSO+IL-4. Bars show mean±standard error of the mean (n=4). RA: retinoic acid, DMSO: dimethylsulfoxide, IL-4: interleukin-4, MCS: pORF -mcs (multiple cloning site). *p<0.05.

• 

  Fig. 2 Immunohistochemical staining of the ears after antipsoriasis treatment experiment. Sections were stained with special antibodies (Psoriasis-associated immunological factors were significant reduced after treatment). Immunohistochemical staining with CD54, CD106, E-selectin, CD31, VEGF and VEGFR-2 of the ears after being treated with the five formulations (RA+DMSO+IL-4; DMSO+IL-4; RA+DMSO+MCS; DMSO+MCS; and saline); Arrows in the images indicate positive cells stained with the corresponding antibody (original magnification ×400). RA: retinoic acid, DMSO: dimethylsulfoxide, IL-4: interleukin-4, VEGF: vascular endothelial growth factor, MCS: pORF-mcs (multiple cloning site).

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