A Novel Effect of Lipids Extracted from Vernix Caseosa on Regulation of Filaggrin Expression in Human Epidermal Keratinocytes

Abstract

Background: Vernix caseosa (VC), which is known as a unique human substance, is a biofilm that covers the skin of most human newborns. VC has many biological functions including anti-infective, skin cleansing and skin barrier repair. Objective: In the study, we purpose to investigate the novel effect of lipids extracted from VC on the regulation of filaggrin (FLG) expression and anti-inflammation in normal human epidermal keratinocyte (NHEK) cells. Methods: The lipids were extracted by chloroform/methanol (Folch method) and the major properties of fatty acid methyl esters were determined with gas chromatography-mass spectrometer. The relative viability of NHEK cells was evaluated by Cell Counting Kit 8 assay. The related expression of skin barrier protein was accessed with real-time quantitative polymerase chain reaction, Western blot and Immunofluorescence in NHEK cells with or without poly (I:C). Meanwhile, the changes of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor alpha (TNF-α) are analyzed by enzyme-linked immunosorbent assay. Results: VC lipids mostly contained saturated and branched chains fatty acids. The expression of mRNA and protein of FLG were significantly increased after the supplement with lipid in NHEK cells. Meanwhile, lipids reversed the inhibition of poly (I:C) on FLG. Moreover, lipids suppressed the over secretion of TSLP and TNF-α induced by poly (I:C). Conclusion: These results indicate that lipids extracted from VC has positive effects on the expression of FLG and anti-inflammation, suggesting that lipids of VC may be used for a reference for novel therapeutic method in reducing and remedying skin disease like atopic disease. (Ann Dermatol 31(6) 611∼620, 2019

Epidermal Immunity and Function: Origin in Neonatal Skin

“…Exposure to vernix lipids attenuated TNFα and TSLP levels, further supporting the antiinflammatory potential of vernix. In this work, keratinocytes treated with Poly I:C decreased FLG expression while the addition of 25, 50, and 100 μg/ml of vernix lipids increased filaggrin (FLG) expression relative to cells that were not treated with Poly I:C. ( Qiao et al, 2019 ). In contrast, FLG expression decreased in keratinocytes that were treated with poly I:C. This work may have broader relevance to newborn infants as FLG is a precursor of the Natural Moisturizing Factor.…”

“…Qiao et al investigated the effects of vernix lipids ( n = 10 infants) on the expression of a critically important skin protein, filaggrin (FLG), and markers of inflammation in normal human epidermal keratinocytes in vitro ( Qiao et al, 2019 ). Inflammation, evidenced by increased amounts of cytokines tumor necrosis factor alpha (TNFα) and thymic stromal lymphopoietin (TSLP) was provoked by exposure of keratinocytes to polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA.…”

“…Inflammation, evidenced by increased amounts of cytokines tumor necrosis factor alpha (TNFα) and thymic stromal lymphopoietin (TSLP) was provoked by exposure of keratinocytes to polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA. This resulted in a dose-dependent reduction in cell viability ( Qiao et al, 2019 ). Exposure to vernix lipids attenuated TNFα and TSLP levels, further supporting the antiinflammatory potential of vernix.…”

The Role of TSLP in Atopic Dermatitis: From Pathogenetic Molecule to Therapeutical Target

“…However, TSLP is not found in nonlesional skin in AD patients and lesions of nickel-induced allergy contact dermatitis or cutaneous lupus erythematosus patients [ 42 ]. In vitro experiments demonstrated that the TSLP expression is significantly elevated in TNF- α -inflamed HaCaT [ 43 ] and ploy (I:C)-induced NHEK cells [ 44 ]. Recent studies hinted that keratinocyte-expressed TSLP is upregulated via TLR [ 45 ] and histamine 4 receptor [ 46 ] while negatively regulated through glucocorticoid receptor [ 47 ] and aryl hydrocarbon receptor [ 48 ].…”

“…In vitro experiments demonstrated that the TSLP expression is significantly elevated in TNF-α-inflamed HaCaT [43] and ploy (I:C)-induced NHEK cells [44]. Recent studies hinted that keratinocyte-expressed TSLP is upregulated via TLR [45] and histamine 4 receptor [46] while negatively regulated through glucocorticoid receptor [47] and aryl hydrocarbon receptor [48].…”