Increased 1-Deoxysphingolipids and Skin BarrierDysfunction in the Skin of X-ray or Ultraviolet BIrradiation and Atopic Dermatitis Lesion Could BePrevented by Moisturizer with Physiological LipidMixture

Background@#Skin diseases characterized by epithelial barrierdysfunction show altered sphingolipid metabolism,which results in changes in the stratum corneum intercellularlipid components and structure. Under pathological conditions,1-deoxysphingolipids form as atypical sphingolipidsfrom de novo sphingolipid biosynthesis. @*Objective@#Thisstudy investigated the potential role of 1-deoxysphingolipidsin skin barrier dysfunction secondary to X-ray and ultravioletB (UVB) irradiation in vitro and in vivo. It was also evaluatedchanges in the expression of 1-deoxysphingolipids in lesionalhuman skin of atopic dermatitis. @*Methods@#In thisstudy, the changes in these 1-deoxysphingolipids levels ofskin and serum samples were investigated in skin barrier dysfunctionassociated with X-ray and UVB irradiation in vitroand in vivo. @*Results@#Increased 1-deoxysphingolipids were observed in cultured normal human epidermal keratinocytesafter X-ray irradiation. X-ray or UVB irradiation increased theproduction of 1-deoxysphingosine in a reconstituted 3-dimensional(3D) skin model. Interestingly, treatment with aphysiological lipid mixture (multi-lamellar emulsion containedpseudoceramide), which can strengthen the epidermalpermeability barrier function, resulted in decreased1-deoxysphingosine formation in a reconstituted 3D skinmodel. Further investigation using a hairless mouse modelshowed similar preventive effects of physiological lipid mixtureagainst 1-deoxysphingosine formation after X-ray irradiation.An increased level of 1-dexoysphingosine in the stratumcorneum was also observed in lesional skin of atopic dermatitis. @*Conclusion@#1-deoxysphingosine might be a novelbiomarker of skin barrier dysfunction and a physiological lipidmixture treatment could prevent 1-deoxysphingosine productionand consequent skin barrier dysfunction.

Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation

PURPOSE: High-affinity receptor I (FcεRI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-FcεRI complex. Thus, prevention of IgE binding to FcεRI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to FcεRI using an antibody targeting FcεRIα. MATERIALS AND METHODS: Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for FcεRIα and effective inhibitory activity against IgE-FcεRI binding were screened. IgE-induced histamine, β-hexosaminidase and Ca2+ release in basophils were determined by ELISA. A B6.Cg-Fcer1a(tm1Knt) Tg(FCER1A)1Bhk/J mouse model of passive cutaneous anaphylaxis (PCA) was used to examine the inhibitory effect of NPB311 on allergic skin inflammation. RESULTS: NPB311 exhibited high affinity to human FcεRIα (KD=4 nM) and inhibited histamine, β-hexosaminidase and Ca2+ release in a concentration-dependent manner in hFcεRI-expressing cells. In hFcεRIα-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with FcεRIα and inhibit the release of inflammation mediators. CONCLUSION: Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/FcεRI-mediated diseases.

Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation

PURPOSE: High-affinity receptor I (FcεRI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-FcεRI complex. Thus, prevention of IgE binding to FcεRI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to FcεRI using an antibody targeting FcεRIα. MATERIALS AND METHODS: Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for FcεRIα and effective inhibitory activity against IgE-FcεRI binding were screened. IgE-induced histamine, β-hexosaminidase and Ca2+ release in basophils were determined by ELISA. A B6.Cg-Fcer1a(tm1Knt) Tg(FCER1A)1Bhk/J mouse model of passive cutaneous anaphylaxis (PCA) was used to examine the inhibitory effect of NPB311 on allergic skin inflammation. RESULTS: NPB311 exhibited high affinity to human FcεRIα (KD=4 nM) and inhibited histamine, β-hexosaminidase and Ca2+ release in a concentration-dependent manner in hFcεRI-expressing cells. In hFcεRIα-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with FcεRIα and inhibit the release of inflammation mediators. CONCLUSION: Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/FcεRI-mediated diseases.

Patterns of acute febrile illness(murine typhus, scrub typhus, leptospirosis and hemorrhagic fever with renal syndrome) from 1986 to 1990 in Korea

No abstract available.