Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol’s effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments.

Psoriasis is a common skin disorder characterized by hyperproliferation and abnormal differentiation of the major cells comprising the skin epidermis, keratinocytes, as well as by skin inflammation. We have previously shown a physical and functional association between the glycerol channel aquaporin‐3 (AQP3) and the enzyme phospholipase D2 (PLD2), which can convert the AQP3‐transported glycerol to phosphatidylglycerol (PG). Further, we have recently demonstrated an ability of PG to inhibit toll‐like receptor‐mediated innate immune system activation by antimicrobial peptides, which are upregulated in psoriasis and can act as danger‐associated molecular patterns to activate toll‐like receptors (TLRs). Glycerol has been reported anecdotally by some patients to improve psoriasis, and we hypothesized that it does so by its PLD2‐mediated conversion to PG. To test this idea, we first demonstrated the ability of topical glycerol to ameliorate inflammation and lesion development in the imiquimod‐induced mouse model of psoriasis. Glycerol reduced ear edema, improved the psoriasis area and severity index (PASI) score, a measure of the appearance and degree of skin lesions, and inhibited the imiquimod‐increased epidermal thickness and tumor necrosis factor‐alpha immunoreactivity. When the same experiment was performed in PLD2 knockout mice, preliminary analysis indicated that glycerol also ameliorated skin lesions; however, topical glycerol is known to function as an emollient, with the capacity to improve skin function and appearance. To overcome this topical glycerol effect, we repeated the experiments using oral glycerol (2% in the drinking water). In the wild‐type mice, oral glycerol again improved the inflammation and skin lesion development induced by imiquimod. On the other hand, there was no significant effect of oral glycerol on these parameters in PLD2 knockout mice. These results provide the first experimental evidence to support the beneficial effects of glycerol in psoriasis. Furthermore, our data suggest that conversion of glycerol to PG underlies in part the glycerol effect and imply that glycerol and/or PG might constitute an effective treatment for this common skin disease.Support or Funding InformationSupported in part by a Research Career Scientist Award and VA Merit Award #CX001357 to WBB. The contents of this article do not represent the official views of the Department of Veterans Affairs or the United States Government.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Various changes in the skin at menopause are based on "so-called dry skin". However, there is no evidence to explain the mechanism. Recently we found decreased hydration, impaired permeability barrier recovery and weakened integrity of the stratum corneum (SC) in an ovariectomized (OVX) mice model of climacterium. These changes in OVX-mice were restored by hormone replacement treatment (HRT) with 17beta-estradiol. The present study was designed to determine whether the dysfunction of the SC in OVX-mice was associated with changes of epidermal differentiation and corneodesmosome. Function of the SC was evaluated in HR mice at 6 weeks after ovariectomy or sham operation with or without HRT. Immediate after functional analysis, skin was taken for further analysis. Thickness of epidermis and dermis were comparable between OVX-and control-mice on HE-section, although those in HRT mice were thicker than others. Immunohistochemistry showed decreased expression of desmoglein-1, KLK7, loricrin, involucrin in OVX-mice compared with those in control-and HRT-mice. Real-time PCR showed increased levels of mRNA of desmoglein-1, KLK7, and SPINK5 in mice with HRT compared with other groups of mice, and those of KLK5 and corneodesmosin were comparable. In conclusion, reduced levels of hydration and impaired permeability barrier function of the SC in OVX-mice might be caused by impaired epidermal differentiation, and weakened integrity of the SC could be related to decreased levels of desmoglein-1, which might be associated with degradation of corneodesmosome. Thus, dysfunction of the SC found in OVX-mice model of climacterium should be a cause of symptom and a target for treatment at menopause.