Soy Phosphatidylglycerol Reduces Inflammation in a Contact Irritant Ear Edema Mouse Model In Vivo

Abstract

We have previously shown that phosphatidylglycerol (PG) regulates the function of keratinocytes, the predominant cells that compose the epidermis, inhibiting the proliferation of rapidly dividing keratinocytes. In particular, soy PG, a PG mixture with a high proportion of polyunsaturated fatty acids, is efficacious at inhibiting these proliferating keratinocytes. Psoriasis is a skin disorder characterized by hyperproliferation of keratinocytes and inflammation. Data in the lung suggest that PG in pulmonary surfactant inhibits inflammation. To investigate the possibility of using PG containing polyunsaturated fatty acids for the treatment of psoriasis, we examined the effect of soy PG on inflammation induced by the application of 12--tetradecanoylphorbol 13-acetate (TPA), a contact irritant, to mouse ears in vivo. We monitored ear thickness and weight as a measure of ear edema, as well as CD45-positive immune cell infiltration. Our results indicate that soy PG when applied together with 1,25-dihydroxyvitamin D (vitamin D), an agent known to acutely disrupt the skin barrier, suppressed ear edema and inhibited the infiltration of CD45-positive immune cells. On the other hand, neither PG nor vitamin D alone was effective. The combination also decreased tumor necrosis factor- (TNF) levels. This result suggested the possibility that PG was not permeating the skin barrier efficiently. Therefore, in a further study we applied PG in a penetration-enhancing vehicle and found that it inhibited inflammation induced by the phorbol ester and decreased CD45-positive immune cell infiltration. Our results suggest the possibility of using soy PG as a topical treatment option for psoriasis.

Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns

“…This result suggests that PG may be an effective therapeutic for treating sterile inflammation, that is, inflammation resulting from noninfectious causes, such as occurs in skin diseases but also in corneal disorders such as chemical burns and dry eye syndrome and in stroke, neurodegenerative diseases, myocardial infarction, and atherosclerosis (Oh et al, 2012). In this regard, we suggest that inhibition of DAMPinduced inflammation may explain the previously observed ability of PG to decrease skin inflammation in response to the contact irritant 12-O-tetradecanoylphorbol 13-acetate (Xie et al, 2018). 12-O-tetradecanoylphorbol 13-acetate is known to up-regulate antimicrobial peptides like S100A8 and S100A9 (Gebhardt et al, 2002;McNeill and Hogg, 2014); therefore, we hypothesize that PG inhibits 12-O-tetradecanoylphorbol 13-acetateeinduced inflammation in this model in part by blocking inflammatory mediator production elicited by 12-O-tetradecanoylphorbol 13-acetateeincreased antimicrobial peptides.…”

“…However, another characteristic of psoriasis is (sterile) inflammation with extensive immune cell infiltration into the skin. Although we have previously shown that PG derived from soy is able to suppress these parameters in a contact irritant ear edema mouse model (Xie et al, 2018), the mechanism by which PG affects skin inflammation remains unknown.…”

“…Psoriasis, an immune-mediated inflammatory skin disorder , is characterized by extensive inflammation in the absence of infection. We recently showed that PG inhibits skin inflammation induced by a contact irritant applied to the ears of mice in vivo (Xie et al, 2018). We reasoned that the ability of the contact irritant to elicit inflammation might be related in part to its capacity to induce antimicrobial peptides (Gebhardt et al, 2002;McNeill and Hogg, 2014), which are known to function as DAMPs to activate TLRs and stimulate the innate immune system to induce inflammation (Erridge, 2010).…”

Preparation of n‐3 Polyunsaturated Phosphatidylglycerol from Salmon Roe Lipids by Phospholipase D and In Vitro Digestion

“…Notably, PG species binding polyunsaturated fatty acids (PUFAs) such as linoleic acid (LA, 18:2n‐6) were found to be effective at inhibiting keratinocyte proliferation, whereas PG species possessing saturated or monounsaturated fatty acids promoted proliferation in slowly dividing keratinocytes . The current study indicated that, soybean PG which mainly contains linoleic acid suppressed inflammation in mouse contact irritant mouse ear edema models . These results suggested that molecular species of PG containing specific fatty acids may regulate keratinocyte growth and inflammation associated with skin diseases.…”

Pathogen-Associated Molecular Pattern-Induced TLR2 and TLR4 Activation Increases Keratinocyte Production of Inflammatory Mediators and is Inhibited by Phosphatidylglycerol

“…Soy PG possesses a large percentage of polyunsaturated fatty acids, with particular efficacy to inhibit keratinocyte proliferation (Xie et al, 2014), suggesting that it might be used to suppress the keratinocyte hyperproliferation characteristic of psoriasis. Indeed, we showed that soy PG inhibits inflammation and mouse ear swelling induced by the contact irritant 12-O-tetradecanoylphorbol 13-acetate in vivo (Xie et al, 2018). However, the mechanism by which soy PG functions to suppress inflammation is unclear.…”