Skin Barrier

Front cover......Page 1
Preface......Page 6
Contents......Page 8
Contributors......Page 18
HOW ARE THE VARIOUS BARRIER FUNCTIONS MEDIATED?......Page 22
EVOLVING CONCEPTS OF THE SC BARRIER......Page 23
PROTECTIVE FUNCTIONS ARE LINKED Co-Localization of Defensive Functions......Page 26
Psychological Stress Alters Both Barrier Function and SC Integrity/Cohesion......Page 29
Elevations of SC pH Can Alter Multiple Defensive Functions......Page 30
Alterations in Mechanical Barrier Influence Permeability Barrier......Page 32
REFERENCES......Page 33
3 A Brief History of How the Dead Stratum Corneum Became Alive......Page 36
CODA......Page 43
REFERENCES......Page 44
INTRODUCTION......Page 46
REFERENCES......Page 51
Major Components......Page 54
Minor Components......Page 56
Covalently Bound Lipids......Page 57
BIOSYNTHETIC PATHWAYS Cholesterol......Page 58
Fatty Acids......Page 59
Ceramides and Glucosylceramides......Page 60
REFERENCES......Page 61
INTRODUCTION......Page 64
WHAT IS A CERAMIDE?......Page 65
Molecular Heterogeneity......Page 66
Localization......Page 68
GENERATION OF STRATUM CORNEUM CERAMIDES Generation of Epidermal Sphingolipids......Page 69
Origins of Stratum Corneum Ceramides......Page 70
THERAPEUTIC APPLICATIONS......Page 74
Ceramide Agents......Page 75
Pseudoceramides......Page 76
Stimulation of Endogenous Ceramide Production......Page 77
REFERENCES......Page 79
INTRODUCTION......Page 86
STRATUM CORNEUM LIPID COMPOSITION AND ORGANIZATION IN NORMAL SKIN Lipid Composition in Stratum Corneum......Page 87
Lipid Organization in Stratum Corneum......Page 89
Lipid Organization in Stratum Corneum with Abnormal Lipid Composition......Page 96
BARRIER FUNCTION IN HUMAN SKIN EQUIVALENTS......Page 99
RELATION BETWEEN LIPID COMPOSITION AND ORGANIZATION The Role of CER, CHOL, and FFA in Lipid Phase Behavior......Page 102
The Role of the Various Ceramide Subclasses in Phase Behavior of SC Lipids......Page 103
Phase Behavior in Mixtures Prepared from Human CER 1–9: The Role of Human CER1......Page 104
Lipid Mixtures Based on Commercially Available and Synthetic Ceramides......Page 105
A UNIQUE MOLECULAR ARRANGEMENT IN THE LONG PERIODICITY PHASE......Page 106
CONCLUSIONS......Page 109
REFERENCES......Page 110
INTRODUCTION......Page 118
THE LIFE-CYCLE OF KERATINOCYTES AND THE HISTO-ARCHITECTURE OF THE EPIDERMIS......Page 119
FORMATION OF THE CE AND THE CLE......Page 121
Mouse Models Designed to Determine ‘‘The Critical Component’’ of the CE......Page 124
CONCLUSIONS AND FUTURE DIRECTIONS......Page 126
REFERENCES......Page 127
INTRODUCTION......Page 132
PROFILAGGRIN / FILAGGRIN The Profilaggrin Pathway......Page 135
Profilaggrin Protein and Gene Structure......Page 136
Profilaggrin Expression and Keratohyalin Granule Formation......Page 137
Profilaggrin Processing to Filaggrin and the N-Terminal Peptide......Page 138
The Multiple Functions of Filaggrin: IFAP, Cornified Envelope Protein, and NMF Components......Page 140
The Profilaggrin N-Terminal Peptide: Structure and Potential Functions......Page 141
Regulation of Profilaggrin Gene Expression......Page 143
Alteration of Profilaggrin / Filaggrin Expression in Disorders of Keratinization......Page 144
Evolutionary Aspects......Page 145
Structure of Mouse Flg-2......Page 146
The Flg-2 Repeats Function as a Keratin-Aggregating Protein......Page 147
TRICHOHYALIN Structure and Function of Trichohyalin......Page 148
REPETIN......Page 149
C1ORF10 (CORNULIN)......Page 150
SUMMARY AND CONCLUDING REMARKS......Page 151
NOTE ADDED IN PROOF......Page 152
REFERENCES......Page 153
KERATIN COMPLEXITY, NOMENCLATURE, AND GENOME ORGANIZATION......Page 162
THE MAMMALIAN KERATIN TYPE I CLUSTERS......Page 163
THE MAMMALIAN KERATIN TYPE II CLUSTERS......Page 166
DOMAIN STRUCTURE, ASSEMBLY, AND PROTEIN MODIFICATIONS......Page 167
GENE REGULATION AND EXPRESSION......Page 169
KERATINOPATHIES......Page 172
KERATINS AND SIGNALING......Page 173
KERATIN KNOCKOUT MICE AND OTHER FUNCTIONAL STUDIES Simple and Embryonic Epithelia......Page 174
Stratified Epithelia......Page 177
Live Cell Imaging......Page 179
CONCLUSIONS AND PERSPECTIVES......Page 180
REFERENCES......Page 181
STRUCTURAL ASPECTS Cell–Cell Junctions in the Human Epidermis......Page 192
Desmosomes......Page 194
Corneodesmosomes: Specialized and Reorganized Desmosomes of the Stratum Corneum......Page 195
Corneodesmosomes in the Hair Follicle......Page 197
BIOCHEMICAL ANALYSIS Components of Corneodesmosomes......Page 198
Corneodesmosin: Structure and Function......Page 200
FUNCTIONAL CORRELATES The Role of Corneodesmosomes in SC Cohesion and Their Orderly Degradation During SC Desquamation......Page 202
Corneodesmosomes in Skin Pathology......Page 205
REFERENCES......Page 207
INTRODUCTION......Page 212
TIGHT JUNCTIONS (TJ) IN SIMPLE EPITHELIA......Page 213
TIGHT JUNCTIONS IN THE SKIN......Page 217
BARRIER FUNCTION OF TJ IN THE SKIN......Page 221
REFERENCES......Page 223
INTRODUCTION......Page 232
IMPACT RESISTANCE OF THE INTEGUMENT......Page 234
PERMEABILITY BARRIER......Page 235
FACULTATIVE WATERPROOFING......Page 236
WHY DO LESSONS FROM COMPARATIVE BIOLOGY MATTER TO THE BARRIER RESEARCHERS?......Page 240
REFERENCES......Page 241
SC pH: MEASUREMENT......Page 244
SC pH: ORIGIN......Page 245
Epidermal Permeability Barrier......Page 246
Antimicrobial Activity and Inflammation......Page 247
REFERENCES......Page 248
LAMELLAR MEMBRANE STRUCTURES IN MAMMALIAN STRATUM CORNEUM......Page 252
GLUCOSYLCERAMIDES AS A MAJOR SOURCE OF STRATUM CORNEUM CERAMIDES......Page 254
Localization of GlcCer’ase in Mammalian Epidermis......Page 256
GLUCOSYLCERAMIDE PROCESSING IS REQUIRED FOR EPIDERMAL BARRIER FUNCTION......Page 257
REGULATION OF GlcCer’ase ACTIVITY IN THE EPIDERMIS AND SC Role of pH......Page 258
Role of Saposins......Page 259
LIPID PROCESSING OF THE CORNEOCYTE LIPID ENVELOPE......Page 260
SPHINGOMYELINASE ACTIVITY IN THE GENERATION OF SC BARRIER LIPIDS......Page 261
PROCESSING OF GLYCEROPHOSPHOLIPIDS BY SECRETORY PHOSPHOLIPASES......Page 263
CERAMIDASES IN EPIDERMAL LIPID PROCESSING AND FUNCTION......Page 264
PROCESSING OF CHOLESTEROL SULFATE BY STEROID SULFATASE......Page 265
LIPID PROCESSING ALTERATIONS IN ATOPIC DERMATITIS......Page 266
ALTERED LIPID PROCESSING IN PSORIASIS......Page 268
ALTERED LIPID PROCESSING WITH AGING......Page 269
REFERENCES......Page 270
Functions Attributed to Lamellar Bodies......Page 282
REGULATION OF LAMELLAR BODY SECRETION Kinetics of LB Secretion......Page 286
Regulation of LB Secretion......Page 287
Structural and Metabolic Adaptations that Facilitate LB Secretion......Page 288
REFERENCES......Page 290
DEVELOPMENT OF HUMAN SKIN......Page 294
PERIDERM—THE EMBRYONIC SKIN LAYER OF UNKNOWN FUNCTION......Page 296
Embryonic Period (Post Gastrulation Embryo to 8 Weeks)......Page 298
Embryonic Fetal Transition (9–10 Weeks, 60–70 Days)......Page 300
Mid Fetal Period (15–20 Weeks)......Page 301
Late Fetal Period (20–40 Weeks)......Page 302
CONCLUSION......Page 304
REFERENCES......Page 305
INTRODUCTION......Page 310
THE EPIDERMAL CALCIUM GRADIENT......Page 311
ALTERED CALCIUM GRADIENT IN SKIN DYSFUNCTIONS......Page 313
CALCIUM GRADIENT AND PERMEABILITY BARRIER: EXPERIMENTAL STUDIES......Page 316
REGULATION OF THE CALCIUM GRADIENT......Page 318
IMPLICATIONS OF EPIDERMAL CALCIUM GRADIENT FOR SKIN BIOLOGISTS......Page 321
REFERENCES......Page 322
INTERLEUKIN-1 FAMILY General......Page 326
IL-1 in the Epidermis......Page 327
TNF and the Epidermis......Page 329
INTERLEUKIN-6 FAMILY General......Page 330
EFFECT OF BARRIER DISRUPTION ON CYTOKINE HOMEOSTASIS IN THE EPIDERMIS......Page 331
ROLE IN BARRIER REPAIR KO Mouse Studies......Page 333
SUMMARY......Page 334
REFERENCES......Page 335
MECHANISM OF ACTION......Page 340
Epidermal Consequences of PPAR-alpha Deficiency......Page 343
In Vitro Effects of PPAR-Alpha in Cultured Human Keratinocytes......Page 344
Anti-inflammatory Effects......Page 345
In Vivo Effects of PPAR-Delta Activation......Page 346
In Vitro Effects of PPAR-Delta in Cultured Human Keratinocytes......Page 347
PPAR-GAMMA......Page 348
In Vitro Effects of PPAR-Gamma in Cultured Human Keratinocytes......Page 349
Epidermal Consequences of LXR Deficiency......Page 350
In Vitro Effects of LXR in Cultured Human Keratinocytes......Page 351
Anti-inflammatory Effects......Page 352
CROSSTALK BETWEEN LIPIDS AND PROTEINS IN THE EPIDERMIS......Page 353
REFERENCES......Page 354
The Corneocyte......Page 358
Regulation of Corneocyte Protein Expression......Page 363
Extracellular Lipids of the SC......Page 364
Corneocyte Lipid Envelope......Page 366
Applications of the Cutaneous Stress Test......Page 367
Regulation of Lipid Synthesis by Barrier Requirements......Page 369
Transcriptional Regulation of Epidermal Lipid Synthesis......Page 370
Barrier Homeostasis Requires Synthesis of Each of the Three Key Lipids......Page 371
The Three Key SC Lipids are Required in an Equimolar Distribution......Page 372
EXTRACELLULAR SIGNALS OF BARRIER HOMEOSTASIS Calcium (Ca) and Other Ions......Page 373
Cytokines and Growth Factors......Page 374
REFERENCES......Page 375
INTRODUCTION......Page 384
SKIN SURFACE pH......Page 385
ANTIMICROBIAL PEPTIDES......Page 386
Defensins......Page 387
Cathelicidins......Page 388
OTHER PROTEINS AND PEPTIDES WITH ANTIMICROBIAL PEPTIDE FUNCTIONS Chemokines......Page 390
Proenkephalin A......Page 391
ENZYMES......Page 392
BARRIER IMPLICATIONS......Page 393
REFERENCES......Page 394
GENERATION OF REACTIVE OXYGEN SPECIES AND OXIDATIVE STRESS......Page 400
PHYSIOLOGICAL BARRIER ANTIOXIDANTS......Page 401
VITAMIN E......Page 402
VITAMIN C, GLUTATHIONE, AND URIC ACID......Page 403
ENZYMATIC ANTIOXIDANTS IN THE STRATUM CORNEUM Interceptive Antioxidant Enzymes......Page 404
IMPACT OF ENVIRONMENTAL FACTORS ON BARRIER ANTIOXIDANTS Ozone......Page 405
UVA and UVB......Page 406
PHYSIOLOGICAL MECHANISMS OF BARRIER ANTIOXIDANT REPLETION Human Sebum Contains High Amounts of Vitamin E......Page 408
Dietary Supplementation of Vitamin E Increases Sebum Vitamin E Levels......Page 409
CLINICAL IMPLICATIONS Photo-Protection......Page 410
Microbial Colonization and Infection......Page 412
Aging......Page 413
REFERENCES......Page 414
INTRODUCTION......Page 420
STRATUM CORNEUM HYDRATION AND WATER CONTENT......Page 422
STRATUM CORNEUM WATER RETENTION CAPACITY......Page 426
STRATUM CORNEUM LIPID AND NMF GRADIENTS......Page 430
THE EFFECT OF THE SEASONS AND ATMOSPHERIC CONDITIONS ON THE STRATUM CORNEUM......Page 431
THE ROLE OF WATER IN THE STRATUM CORNEUM......Page 435
CONCLUSIONS......Page 441
REFERENCES......Page 443
VITAMIN D PRODUCTION AND METABOLISM IN THE EPIDERMIS Vitamin D3 Production......Page 448
Metabolism of D3 to its Biologically Active Products......Page 450
ROLE OF VITAMIN D3 IN EPIDERMAL DIFFERENTIATION The Differentiation Process......Page 452
Regulation of Differentiation by Calcium......Page 453
1,25(OH)2D-Regulated Proliferation and Differentiation: Interactions with Calcium......Page 456
REFERENCES......Page 458
INTRODUCTION......Page 468
IN VIVO FUNCTIONAL ASSESSMENT OF THE SC BARRIER......Page 469
MEASUREMENTS OF SKIN SURFACE HYDRATION STATE......Page 470
Inflammatory Dermatoses......Page 471
Hereditary Keratinization Disorders......Page 479
SC CHANGES THAT OCCUR LATER IN LIFE IN THOSE WITH NORMAL HEALTHY SKIN......Page 481
CONCLUDING REMARKS......Page 483
REFERENCES......Page 484
INTRODUCTION Normal Epidermal Differentiation and Cornification......Page 490
Pathogenesis—Permeability Barrier as End Product of Cornification......Page 496
Inherited Abnormalities of Lipid Metabolism......Page 498
Acquired Ichthyoses Due to Lipid Abnormalities......Page 506
ABNORMALITIES OF CORNEOCYTES......Page 507
Inherited Abnormalities of CE Proteins......Page 508
ABNORMALITIES IN INTERCELLULAR COMMUNICATION (GAP JUNCTIONS)......Page 516
ABNORMALITIES IN CORNEOCYTE COHESION DUE TO ABNORMAL PROTEOLYSIS OF DESMOSOMES......Page 518
REFERENCES......Page 519
THE MOLECULAR AND BIOCHEMICAL BASIS FOR RECESSIVE X-LINKED ICHTHYOSIS......Page 532
STEROID SULFATASE AND CHOLESTEROL SULFATE IN NORMAL EPIDERMAL PHYSIOLOGY......Page 533
REGULATION OF DIFFERENTIATION BY CHOLESTEROL SULFATE......Page 534
MECHANISMS PROPOSED AS CAUSES OF ABNORMAL DESQUAMATION IN RXLI......Page 535
REFERENCES......Page 536
INTRODUCTION......Page 540
Practical Aspects......Page 541
PRIMARY INDIVIDUAL PREVENTION......Page 542
Skin Protection via Occlusion......Page 543
Hyper-Reactivity of the Skin......Page 544
Percutaneous Absorption......Page 546
Antioxidant......Page 547
SECONDARY INDIVIDUAL PREVENTION......Page 548
TERTIARY INDIVIDUAL PREVENTION......Page 550
REFERENCES......Page 551
Chol and FA Syntheses......Page 556
Regulation of Sphingolipid Metabolism......Page 557
Growth Factors......Page 558
THE AGED EPIDERMAL BARRIER Functional Changes in Chronologic and Photoaged Skin......Page 559
Structural Basis for the Aged Permeability Barrier......Page 562
Metabolic and Regulatory Basis for the Aged Barrier Abnormality......Page 563
Molecular Mechanisms Mediating Epidermal Aging......Page 565
BARRIER REPAIR STRATEGIES FOR AGED EPIDERMIS......Page 566
CLINICAL IMPLICATIONS......Page 567
REFERENCES......Page 568
INTRODUCTION......Page 574
Immobilization-Induced Stress (24)......Page 575
New Environment-Induced Stress (31)......Page 576
Metabolic Bases for the Barrier Abnormality......Page 578
HUMAN EXPERIMENTS (33)......Page 580
Long Period of Stress (36)......Page 581
EPIDERMIS AND ENDOCRINE SYSTEM......Page 583
EPIDERMIS AND NEUROTRANSMITTERS......Page 584
CONCLUSION......Page 585
REFERENCES......Page 586
NORMAL STRATUM CORNEUM: COMPOSITION AND FUNCTION......Page 590
ATOPIC DERMATITIS: GENETICS......Page 591
Hydration......Page 592
Lipids......Page 593
Proliferation and Differentiation......Page 597
CLINICAL MANIFESTATIONS RESULTING FROM IMPAIRED BARRIER FUNCTION......Page 599
Contact Allergies......Page 600
THERAPEUTIC IMPLICATIONS......Page 601
REFERENCES......Page 602
DYNAMICS OF BARRIER RECOVERY......Page 612
CLINICAL APPLICATIONS OF THE CUTANEOUS STRESS TEST......Page 613
NON-PHYSIOLOGIC LIPIDS—MECHANISM OF ACTION......Page 614
POTENTIAL OF BARRIER REPAIR THERAPY......Page 616
REFERENCES......Page 618
Index......Page 622
Back cover......Page 634