Characterization of a Hapten-Induced, Murine Model with Multiple Features of Atopic Dermatitis: Structural, Immunologic, and Biochemical Changes following.

Slides:

Advertisements

Similar presentations

Basis for Enhanced Barrier Function of Pigmented Skin

Advertisements

Serine Protease Signaling of Epidermal Permeability Barrier Homeostasis Jean-Pierre Hachem, Evi Houben, Debra Crumrine, Mao-Quiang Man, Nanna Schurer,

Negative Electric Potential Induces Alteration of Ion Gradient and Lamellar Body Secretion in the Epidermis, and Accelerates Skin Barrier Recovery After.

Deficiency of PPARβ/δ in the Epidermis Results in Defective Cutaneous Permeability Barrier Homeostasis and Increased Inflammation Mao-Qiang Man, Grant.

Peter M. Elias, Sung K. Ahn, Mitsuhiro Denda, Barbara E

Roshan Gunathilake, Nanna Y. Schurer, Brenda A

Topical Liver X Receptor Activators Accelerate Postnatal Acidification of Stratum Corneum and Improve Function in the Neonate Joachim W. Fluhr, Debra.

Omega-Hydroxyceramides are Required for Corneocyte Lipid Envelope (CLE) Formation and Normal Epidermal Permeability Barrier Function Martin Behne, Yoshikazu.

25 Hydroxyvitamin D 1 α-Hydroxylase Is Required for Optimal Epidermal Differentiation and Permeability Barrier Homeostasis D.D. Bikle, S. Chang, D. Crumrine,

Topical Peroxisome Proliferator Activated Receptor-α Activators Reduce Inflammation in Irritant and Allergic Contact Dermatitis Models1 Mary Y. Sheu,

Christina A. Young, Richard L

Caspase-14-Deficient Mice Are More Prone to the Development of Parakeratosis Esther Hoste, Geertrui Denecker, Barbara Gilbert, Filip Van Nieuwerburgh,

Shao Jun Jiang, Sang Min Hwang, Eung Ho Choi, Sung Ku Ahn

Rottlerin, a Specific Inhibitor of Protein Kinase C-delta, Impedes Barrier Repair Response by Increasing Intracellular Free Calcium Bong K. Ahn, Se K.

Formation of the Epidermal Calcium Gradient Coincides with Key Milestones of Barrier Ontogenesis in the Rodent Peter M. Elias, Patricia Nau, Karen Hanley,

Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens Tiffany C. Scharschmidt,

Recessive x-Linked Ichthyosis: Role of Cholesterol-Sulfate Accumulation in the Barrier Abnormality Elizabeth Zettersten, Mao-Qiang Man, Angela Farrell,

Serine Protease Activity and Residual LEKTI Expression Determine Phenotype in Netherton Syndrome Jean-Pierre Hachem, Fredrik Wagberg, Matthias Schmuth,

Mite and Cockroach Allergens Activate Protease-Activated Receptor 2 and Delay Epidermal Permeability Barrier Recovery Se Kyoo Jeong, Hyun Jeong Kim,

Matthias Schmuth, Gil Yosipovitch, Mary L

Vitamin D Receptor and Coactivators SRC2 and 3 Regulate Epidermis-Specific Sphingolipid Production and Permeability Barrier Formation Yuko Oda, Yoshikazu.

Generation of Free Fatty Acids from Phospholipids Regulates Stratum Corneum Acidification and Integrity Joachim W. Fluhr, Jack Kao, Sung K. Ahn, Kenneth.

Eung-Ho Choi, Mao-Qiang Man, Pu Xu, Shujun Xin, Zhili Liu, Debra A

Maintenance of an Acidic Stratum Corneum Prevents Emergence of Murine Atopic Dermatitis Yutaka Hatano, Mao-Qiang Man, Yoshikazu Uchida, Debra Crumrine,

Barrier Function in Transgenic Mice Overexpressing K16, Involucrin, and Filaggrin in the Suprabasal Epidermis Richard B. Presland, Pierre A. Coulombe,

Topical Hesperidin Enhances Epidermal Function in an Aged Murine Model

Origin of the Corneocyte Lipid Envelope (CLE): Observations in Harlequin Ichthyosis and Cultured Human Keratinocytes Peter M. Elias, Manigé Fartasch,

Vitamin C Stimulates Sphingolipid Production and Markers of Barrier Formation in Submerged Human Keratinocyte Cultures Yoshikazu Uchida, Martin Behne,

Expression of Epidermal CAMP Changes in Parallel with Permeability Barrier Status Marina Rodriguez-Martin, Gemma Martin-Ezquerra, Mao-Qiang Man, Melanie.

Joachim W. Fluhr, Man Mao-Qiang, Barbara E. Brown, Philip W

Ablation of the Calcium-Sensing Receptor in Keratinocytes Impairs Epidermal Differentiation and Barrier Function Chia-Ling Tu, Debra A. Crumrine, Mao-Qiang.

Histamine H1 and H2 Receptor Antagonists Accelerate Skin Barrier Repair and Prevent Epidermal Hyperplasia Induced by Barrier Disruption in a Dry Environment

Basis for Improved Permeability Barrier Homeostasis Induced by PPAR and LXR Activators: Liposensors Stimulate Lipid Synthesis, Lamellar Body Secretion,

Edward Hsia, Michael J. Johnston, Robert J. Houlden, Wendy H

Low-Frequency Sonophoresis: Ultrastructural Basis for Stratum Corneum Permeability Assessed Using Quantum Dots Sumit Paliwal, Gopinathan K. Menon, Samir.

Paradoxical Benefits of Psychological Stress in Inflammatory Dermatoses Models Are Glucocorticoid Mediated Tzu-Kai Lin, Mao-Qiang Man, Juan-Luis Santiago,

Testosterone Perturbs Epidermal Permeability Barrier Homeostasis

Abnormal Epidermal Barrier Recovery in Uninvolved Skin Supports the Notion of an Epidermal Pathogenesis of Psoriasis Li Ye, Chengzhi Lv, George Man,

Biopositive Effects of Low-Dose UVB on Epidermis: Coordinate Upregulation of Antimicrobial Peptides and Permeability Barrier Reinforcement Seung P. Hong,

Joachim W. Fluhr, Man Mao-Qiang, Barbara E

Short-Term Glucocorticoid Treatment Compromises Both Permeability Barrier Homeostasis and Stratum Corneum Integrity: Inhibition of Epidermal Lipid Synthesis.

Combined Benefits of a PAR2 Inhibitor and Stratum Corneum Acidification for Murine Atopic Dermatitis Takashi Sakai, Yutaka Hatano, Haruna Matsuda-Hirose,

Roshan Gunathilake, Matthias Schmuth, Tiffany C

Topical Peroxisome Proliferator Activated Receptor Activators Accelerate Postnatal Stratum Corneum Acidification Joachim W. Fluhr, Mao-Qiang Man, Jean-Pierre.

Sustained Serine Proteases Activity by Prolonged Increase in pH Leads to Degradation of Lipid Processing Enzymes and Profound Alterations of Barrier Function.

Water Distribution and Natural Moisturizer Factor Content in Human Skin Equivalents Are Regulated by Environmental Relative Humidity Joke A. Bouwstra,

Exposure to a Dry Environment Enhances Epidermal Permeability Barrier Function Mitsuhiro Denda, Junko Sato, Yoshiko Masuda, Toru Tsuchiya, Junichi Koyama,

The “Caveolae Brake Hypothesis” and the Epidermal Barrier

Junko Sato, Mitsuhiro Denda, PhD, Sandra Chang, Peter M

Cellular Changes that Accompany Shedding of Human Corneocytes

Permeability Barrier Disorder in Niemann–Pick Disease: Sphingomyelin–Ceramide Processing Required for Normal Barrier Homeostasis Matthias Schmuth, Mao-Qiang.

Acute Acidification of Stratum Corneum Membrane Domains Using Polyhydroxyl Acids Improves Lipid Processing and Inhibits Degradation of Corneodesmosomes

Barrier Function, Epidermal Differentiation, and Human β-Defensin 2 Expression in Tinea Corporis Jens-Michael Jensen, Stephan Pfeiffer, Tatsuya Akaki,

Basis For Abnormal Desquamation And Permeability Barrier Dysfunction in RXLI Peter M. Elias, Debra Crumrine, Ulrich Rassner, Jean-Pierre Hachem, Gopinathan.

Structural and Functional Consequences of Loricrin Mutations in Human Loricrin Keratoderma (Vohwinkel Syndrome with Ichthyosis) Matthias Schmuth, Joachim.

Pathogenesis-Based Therapy Reverses Cutaneous Abnormalities in an Inherited Disorder of Distal Cholesterol Metabolism Amy S. Paller, Maurice A.M. van.

Origin of the Epidermal Calcium Gradient: Regulation by Barrier Status and Role of Active vs Passive Mechanisms Peter M. Elias, MD., Barbara E. Brown,

Topical Antihistamines Display Potent Anti-Inflammatory Activity Linked in Part to Enhanced Permeability Barrier Function Tzu-Kai Lin, Mao-Qiang Man,

Extracellular pH Controls NHE1 Expression in Epidermis and Keratinocytes: Implications for Barrier Repair J.-P. Hachem, M. Behne, I. Aronchik, M. Demerjian,

The Adverse Effect of IFN Gamma on Stratum Corneum Structure and Function in Psoriasis and Atopic Dermatitis Kenneth R. Feingold Journal of Investigative.

Barrier Dysfunction and Pathogenesis of Neutral Lipid Storage Disease with Ichthyosis (Chanarin–Dorfman Syndrome) Marianne Demerjian, Debra A. Crumrine,

PH Directly Regulates Epidermal Permeability Barrier Homeostasis, and Stratum Corneum Integrity/Cohesion Jean-Pierre Hachem, Debra Crumrine, Joachim.

Stratum Corneum Acidification in Neonatal Skin: Secretory Phospholipase A2 and the Sodium/Hydrogen Antiporter-1 Acidify Neonatal Rat Stratum Corneum

Mitsuhiro Denda, PhD, Shigeyoshi Fuziwara, Kaori Inoue

Eung Ho Choi, Mao-Qiang Man, Fusheng Wang, Xinjiang Zhang, Barbara E

Gopinathan K. Menon Journal of Investigative Dermatology

The Neuroendocrine Peptide Catestatin Is a Cutaneous Antimicrobial and Induced in the Skin after Injury Katherine A. Radek, Belen Lopez-Garcia, Melanie.

Epidermal-Specific Defect of GPI Anchor in Pig-a Null Mice Results in Harlequin Ichthyosis-Like Features Mariko Hara-Chikuma, Junji Takeda, Masahito.

Hyaluronan–CD44 Interaction Stimulates Keratinocyte Differentiation, Lamellar Body Formation/Secretion, and Permeability Barrier Homeostasis Lilly Y.W.

Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis Peter M. Elias, MD, Joan S. Wakefield

Presentation transcript:

Characterization of a Hapten-Induced, Murine Model with Multiple Features of Atopic Dermatitis: Structural, Immunologic, and Biochemical Changes following Single Versus Multiple Oxazolone Challenges Mao-Qiang Man, Yutaka Hatano, Seung H. Lee, Mona Man, Sandra Chang, Kenneth R. Feingold, Donald Y.M. Leung, Walter Holleran, Yoshikazu Uchida, Peter M. Elias Journal of Investigative Dermatology Volume 128, Issue 1, Pages 79-86 (January 2008) DOI: 10.1038/sj.jid.5701011 Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Functional abnormalities emerge after multiple Ox Challenges. (a) SC hydration assessed as electrical capacitance, in absolute units. (b) Surface pH assessed with a flat surface electrode. (c) Permeability barrier function, assessed as changes in basal TEWL with an electrolytic water analyzer (as mg/cm2/hour). (d) Kinetics of permeability barrier recovery after acute barrier disruption by cellophane tape stripping (initial TEWL is increased to 20- to 30-fold above basal levels). Journal of Investigative Dermatology 2008 128, 79-86DOI: (10.1038/sj.jid.5701011) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Repeated Ox challenges alter stratum corneum lipid content/distribution. Cohorts of hairless mice (n=5 each) were treated with vehicle alone, or Ox (1 or 10 applications). Lipids were extracted from isolated stratum corneum sheets with Bligh–Dyer solvents, fractionated, quantified, and the content of each fraction was expressed as μg/mg dry SC weight. Data were expressed as % change from vehicle-treated±SEM. Journal of Investigative Dermatology 2008 128, 79-86DOI: (10.1038/sj.jid.5701011) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Repeat Ox-challenged SC displays entombed lamellar bodies, lamellar membrane disorganization, and corneocyte detachment. (a) Lamellar bodies (LBs) accumulate in the peripheral cytosol of granular cells in Ox-challenged mice (arrows), while (b) LB are more widely dispersed in preparation for secretion in vehicle (Veh)-treated mice. (c) Ox-challenged corneocytes (SC) focally detach from underlying stratum granulosum (SG) and lose contact between themselves (open arrows), sometimes leading to large cleavage planes (asterisk). Decreased quantities and poor organization of extracellular lamellar membranes are seen in Ox-challenged (d, single arrows) versus vehicle-treated (e, layered arrows) mice. Note entombed organelle remnants in corneocyte cytosol of Ox-challenged mice, indicating incomplete LB secretion (d, open arrows). (a–c) Osmium tetroxide post-fixation; (d, e) ruthenium tetroxide post-fixation. Bars=1μm (a–c); 0.1μm (d, e). Journal of Investigative Dermatology 2008 128, 79-86DOI: (10.1038/sj.jid.5701011) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Th2 immunophenotype predominates after repeated Ox challenges. (a) CRTH2 immunostaining of Th2 lymphocytes is virtually absent in dermis after (a) vehicle treatment alone or (b) one Ox challenge, but density of CRTH2-positive cells increases significantly after 10 challenges (c, arrows). Merged images with propidium iodide secondary staining in 5μm frozen sections. Bar=40μm. Journal of Investigative Dermatology 2008 128, 79-86DOI: (10.1038/sj.jid.5701011) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Antimicrobial peptide expression declines after one Ox challenge, and remains reduced after 10 challenges. Immunofluorescent staining for (a–c) cathelicidin-related antimicrobial peptide (CRAMP) and (d–f) mouse β-defensin 3 (mBD3). (a, d) With vehicle treatment; (b, e) with one Ox challenge; (c, f) with 10 Ox challenges. Propidium iodide counterstaining. Bars=20μm. Journal of Investigative Dermatology 2008 128, 79-86DOI: (10.1038/sj.jid.5701011) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions