Journal ArticleDOI
Incontinentia pigmenti: A review and update on the molecular basis of pathophysiology
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TLDR
In this article, the authors present a review of the latest research findings on eosinophil recruitment through eotaxin release by activated keratinocytes and discuss anhidrotic ectodermal dysplasia with immunodeficiency, a disorder allelic to incontinentia pigmenti.Abstract:
Incontinentia pigmenti is an uncommon X-linked dominant disorder, lethal in the majority of affected males in utero and variably expressed in females. Cutaneous manifestations are classically subdivided into 4 stages: vesicular, verrucous, hyperpigmented, and atrophic. Various hair and nail abnormalities, dental anomalies, and ophthalmologic and neurologic deficits are associated with the disorder. The gene for incontinentia pigmenti has been mapped to Xq28. Recently, mutations in the NEMO/IKK γ gene located at Xq28 have been found to cause expression of the disease. Knockout mice heterozygous for NEMO/IKK γ gene deficiency develop a clinical phenotype very similar to that of incontinentia pigmenti. NEMO/IKKγ is an essential component of the newly discovered nuclear factor κB (NF-κB) signaling pathway. When activated, NF-κB controls the expression of multiple genes, including cytokines and chemokines, and protects cells against apoptosis. The mechanism by which NEMO/IKKγ deficiency causes, via the NF-κB pathway, the phenotypical expression of the disease has recently been elucidated. In addition, the newest research findings on eosinophil recruitment through eotaxin release by activated keratinocytes are described in the review. Finally, anhidrotic ectodermal dysplasia with immunodeficiency, a disorder allelic to incontinentia pigmenti, is discussed together with implications on the current understanding of NF-κB function. (J Am Acad Dermatol 2002;47:169-87.) Learning objective: At the completion of this learning activity, participants will have a comprehensive and current understanding of incontinentia pigmenti, including its typical and uncommon clinical and histopathologic characteristics, diagnostic assessment, and current management strategies. Additionally, participants will gain the most current knowledge of the genetic and molecular basis of cutaneous pathomechanism.read more
Citations
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Regulation of tissue homeostasis by NF-κB signalling: implications for inflammatory diseases
TL;DR: Findings indicate that NF-κB signalling acts in non-immune cells to control the maintenance of tissue immune homeostasis and prevents the pathogenesis of inflammatory diseases.
Journal ArticleDOI
Mutations in the NF-kappaB signaling pathway: implications for human disease.
G Courtois,Thomas D. Gilmore +1 more
TL;DR: This review describes human diseases in which mutations in the components of the core NF-κB signaling pathway have been implicated and discusses the molecular mechanisms by which these alterations in NF-σB signaling are likely to contribute to the disease pathology.
Journal ArticleDOI
Towards a new classification of ectodermal dysplasias
TL;DR: The EDs are reviewed in light of the recent molecular and biochemical findings and an attempt is made to classify ED causative genes into four major functional subgroups: cell–cell communication and signalling; adhesion; transcription regulation; and development.
Journal ArticleDOI
Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
Yuumi Nakamura,Naotomo Kambe,Megumu K. Saito,Ryuta Nishikomori,Yun Gi Kim,Makoto Murakami,Gabriel Núñez,Hiroyuki Matsue +7 more
TL;DR: These findings implicate mast cells (MCs) as IL-1β producers in the skin and mediators of histamine-independent urticaria through the NLRP3 inflammasome.
Journal ArticleDOI
The interplay of IKK, NF-κB and RIPK1 signaling in the regulation of cell death, tissue homeostasis and inflammation
TL;DR: Evidence that the regulation of cell death signaling plays an important role in the maintenance of tissue homeostasis is provided, and it is suggested that cell death could be causally involved in the pathogenesis of inflammatory diseases.
References
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Journal ArticleDOI
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights
TL;DR: The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases.
Journal ArticleDOI
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Journal ArticleDOI
Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.
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Journal ArticleDOI
An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
Amer A. Beg,David Baltimore +1 more
TL;DR: Reintroduction of RelA into RelA−/− fibroblasts resulted in enhanced survival, demonstrating that the presence ofrelA is required for protection from TNF-α.
Journal ArticleDOI
Dissection of TNF Receptor 1 Effector Functions: JNK Activation Is Not Linked to Apoptosis While NF-κB Activation Prevents Cell Death
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