The 15d‑PGJ2 hydrogel ameliorates atopic dermatitis through suppression of the immune response

Abstract

The present study examined the efficacy of the topical 15d-PGJ 2 -poloxamer 407 hydrogel in an atopic dermatitis (AD) animal model. The 15d-PGJ 2 hydrogel was prepared and characterized. The examined rats possessed AD-Like cutaneous lesions, which were induced using 2,4-dinitrochlorobenzene, the rats were then treated with a hydrogel vehicle, 15d-PGJ 2 hydrogel or tacrolimus for 14 days. The rats were sacrificed and blood samples were collected to quantify the IgE levels. Subsequently, skin biopsies were stained with toluidine blue to identify mast cells and immunohistochemistry was performed for ROR-γt and TNF-α. Histological analyses demonstrated that 15d-PGJ 2 hydrogel significantly decreased mast cell infiltration (P<0.05) when compared with the AD-group. Tacrolimus at 0.1% exhibited decreased mast cell infiltration; however, this difference was not statistically significant from the AD-group. Topical 15d-PGJ 2 hydrogel and Tacrolimus 0.1% significantly reduced the serum levels of IgE (P<0.05) compared with the AD-group. Immunohistochemistry revealed a significant decrease in ROR-γt and TNF-α positive cell expression (P<0.05) in the 15d-PGJ 2 hydrogel group compared with the AD-group. In summary, topical administration of 15d-PGJ 2 hydrogel had a beneficial effect on AD symptoms, suggesting that this formulation may be a useful strategy for the treatment of AD.

Epidermal PPARγ Is a Key Homeostatic Regulator of Cutaneous Inflammation and Barrier Function in Mouse Skin

“…As seen in Figure 2C and Figure S3B, with the exception of one transcript (Il31ra), all of the top regulated pro-inflammatory transcripts were increased by loss of epidermal Pparg. This supports previous reports that PPARγ agonists have anti-inflammatory activity in skin [5,[18][19][20][21][22][23][24][25][26]. It also indicates that epidermal PPARγ serves as a key modulator of baseline cutaneous inflammatory signaling.…”

“…However, in mouse models of atopic dermatitis, results have been inconclusive. Several groups reported improvements in eczematous lesions following topical application of PPARγ ligands either alone [23], or in combination with glucocorticoids [24]. However, other groups failed to show therapeutic efficacy of topical PPARγ agonists in mouse models of atopic dermatitis [25,26].…”

Hydrogels: A Promising Vehicle for the Topical Management of Atopic Dermatitis

“…Improved naringenin skin permeation [65] Rhus verniciflua extract Pullulan Lower IgE [66] Cynaroside Sodium alginate, glycerol, and propylene glycol. Reduction of IL-4; Lower IgE [67] Tacrolimus Carbomer, carnoside, and transcutol P Higher skin permeation compared to reference ointment [68] 15d-PGJ2 prostaglandin Poloxamer 407 Lower IgE [71] Polyvinyl-pyrrolidone iodine Phospholipone liposomes incorporated in a carbopol hydrogel.…”

“…[ 70 ] Due to its potential efficacy, it was incorporated in a thermoreversible hydrogel formed by poloxamer 407 and tested in 2,4‐dinitrochlorobenzene‐induced AD male Wistar rats. [ 71 ] The formulation had an extended release profile, reduced mast cell infiltration in skin, and decreased systemic IgE levels.…”

Topical Administration of 15-Deoxy-Δ12,14-Prostaglandin J2 Using a Nonionic Cream: Effect on UVB-Induced Skin Oxidative, Inflammatory, and Histopathological Modifications in Mice

“…In terms of anti-inflammatory response, a topical poloxamer hydrogel containing 15d-PGJ 2 reduced atopic dermatitis-like disease caused by topical administration of 2,4-dinitrochlorobenzene in mice. The mechanisms of 15d-PGJ 2 hydrogel involved the reduction of immunostaining of ROR- γ t and TNF- α , which suggest a reduction of adaptive immunity with reduced Th17 lymphocytes [ 5 ]. Opposing to these data, it was found that 15d-PGJ 2 can work as a neuritogenic promoter by activating TRPV1 channels and enhancing NGF activity, which ultimately aggravates atopic dermatitis [ 6 ].…”