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1.
Cureus ; 16(2): e54751, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38523953

ABSTRACT

Secukinumab (Cosentyx), an interleukin-17A-targeting biological agent, is commonly prescribed for psoriasis, psoriatic arthritis, and spondyloarthritis (SpA). Alopecia areata (AA), an IL-17-mediated autoimmune disorder characterized by nonscarring hair loss, particularly in an ophiasis pattern, represents a rare adverse effect associated with secukinumab therapy. We present a case of a 46-year-old female with SpA undergoing secukinumab treatment, who developed an ophiasis pattern of AA, subsequently experiencing regrowth upon medication discontinuation. The patient's clinical course and treatment response are detailed, alongside a discussion on the potential pathophysiological mechanisms underlying secukinumab-induced AA. Additionally, we provide a review of existing literature, discussing similar cases and proposing hypotheses on the immunological basis of this adverse event. This report underscores the importance of recognizing and managing secukinumab-induced AA, highlighting the need for further investigation and tailored therapeutic approaches in affected patients.

2.
Dermatol Clin ; 42(2): 231-245, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423684

ABSTRACT

Neutrophilic dermatoses are a broadly heterogeneous group of inflammatory skin disorders. This article reviews 5 conditions: amicrobial pustulosis of the folds, aseptic abscess syndrome, Behçet disease, neutrophilic eccrine hidradenitis, and pyostomatitis vegetans-pyodermatitis vegetans.The authors include up-to-date information about their epidemiology, pathogenesis, clinicopathologic features, diagnosis, and management.


Subject(s)
Behcet Syndrome , Hidradenitis , Pemphigus , Humans , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Abscess/diagnosis , Abscess/drug therapy , Skin/pathology , Hidradenitis/pathology , Organic Chemicals
3.
Front Immunol ; 14: 1173035, 2023.
Article in English | MEDLINE | ID: mdl-37197667

ABSTRACT

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint expressed in regulatory T (Treg) cells and activated T lymphocytes. Despite its potential as a treatment strategy for melanoma, CTLA-4 inhibition has limited efficacy. Using data from The Cancer Genome Atlas (TCGA) melanoma database and another dataset, we found that decreased CTLA4 mRNA was associated with a poorer prognosis in metastatic melanoma. To investigate further, we measured blood CTLA4 mRNA in 273 whole-blood samples from an Australian cohort and found that it was lower in metastatic melanoma than in healthy controls and associated with worse patient survival. We confirmed these findings using Cox proportional hazards model analysis and another cohort from the US. Fractionated blood analysis revealed that Treg cells were responsible for the downregulated CTLA4 in metastatic melanoma patients, which was confirmed by further analysis of published data showing downregulated CTLA-4 surface protein expression in Treg cells of metastatic melanoma compared to healthy donors. Mechanistically, we found that secretomes from human metastatic melanoma cells downregulate CTLA4 mRNA at the post-transcriptional level through miR-155 while upregulating FOXP3 expression in human Treg cells. Functionally, we demonstrated that CTLA4 expression inhibits the proliferation and suppressive function of human Treg cells. Finally, miR-155 was found to be upregulated in Treg cells from metastatic melanoma patients compared to healthy donors. Our study provides new insights into the underlying mechanisms of reduced CTLA4 expression observed in melanoma patients, demonstrating that post-transcriptional silencing of CTLA4 by miRNA-155 in Treg cells may play a critical role. Since CTLA-4 expression is downregulated in non-responder melanoma patients to anti-PD-1 immunotherapy, targeting miRNA-155 or other factors involved in regulating CTLA4 expression in Treg cells without affecting T cells could be a potential strategy to improve the efficacy of immunotherapy in melanoma. Further research is needed to understand the molecular mechanisms regulating CTLA4 expression in Treg cells and identify potential therapeutic targets for enhancing immune-based therapies.


Subject(s)
Melanoma , MicroRNAs , Neoplasms, Second Primary , Humans , T-Lymphocytes, Regulatory , CTLA-4 Antigen , Australia , Prognosis , MicroRNAs/metabolism
4.
J Nutr Sci Vitaminol (Tokyo) ; 68(1): 32-38, 2022.
Article in English | MEDLINE | ID: mdl-35228493

ABSTRACT

Type 2 diabetes mellitus (T2DM) has been increasing rapidly in Vietnam as well as world-wide. One of the major causes of the condition is low fiber intake. It is difficult to eat large amounts of vegetables every day to reach a sufficient amount of fiber but Textured Soybean Protein is rich in fiber. The study aimed to examine the effectiveness of Textured Soybean Protein consumption on T2DM patients. In this randomized controlled trial, 47 T2DM patients were divided into an intervention group (n=24) and a control group (n=23). The intervention group were asked to consume 40 g Textured Soybean Protein in 2 dishes for 4 wk. The control group continued their usual diet. Fasting blood samples were drawn before and after intervention to measure fasting plasma glucose (FPG), fructosamine, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), total cholesterol (T-C), and triglycerides (TG). A 3-day food record was conducted at 1 wk before (baseline) and at the last week (final) of the intervention period. In the Textured Soybean Protein consumption group, there was a significant decrease in fructosamine (363±86 µmol/L to 347±82 µmol/L, p=0.03), T-C (5.2±0.9 mmol/L to 4.8±0.8 mmol/L, p=0.02) and TG (3.5±2.2 mmol/L to 2.8±2.0 mmol/L, p=0.02). Total energy intake in the two groups did not change significantly. There was a shift in the dietary pattern of the Textured Soybean Protein consumption group; lipid intake showed a significant decrease (p=0.001) and fiber intake increased by 6 g (p<0.001). The consumption of Textured Soybean Protein in the diet could have favorable effects in improving glycemic and lipid concentrations in T2DM patients.


Subject(s)
Diabetes Mellitus, Type 2 , Soybean Proteins , Asian People , Blood Glucose/metabolism , Cholesterol, HDL , Humans , Glycine max , Triglycerides
5.
Cancer Control ; 26(1): 1073274819865274, 2019.
Article in English | MEDLINE | ID: mdl-31331188

ABSTRACT

The population size and projected demographics of Vietnam's 2 largest cities, Ho Chi Minh City (HCMC) and Hanoi, will change dramatically over the next decade. Demographic changes in an aging population coupled with income growth and changes in lifestyle will result in a very different distribution of common cancers in the future. The study aimed to project the number of cancer incidence in the 2 largest populated cities in Vietnam for the year 2025. Cancer incidence data from 2004 to 2013 collected from population-based cancer registries in these 2 cities were provided by Vietnam National Cancer Institute. Incidence cases in 2013 and the previous decades average annual percent changes of age-standardized cancer incidence rates combined with expected population growth were modeled to project cancer incidence for each cancer site by gender to 2025. A substantial double in cancer incidence from 2013 to 2025 resulted from a growing and aging population in HCMC and Hanoi. Lung, colorectum, breast, thyroid, and liver cancers, which represent 67% of the overall cancer burden, are projected to become the leading cancer diagnoses by 2025 regardless of genders. For men, the leading cancer sites in 2025 are predicted to be lung, colorectum, esophagus, liver, and pharynx cancer, and among women, they are expected to be breast, thyroid, colorectum, lung, and cervical cancer. We projected an epidemiological transition from infectious-associated cancers to a high burden of cancers that have mainly been attributed to lifestyle in both cities. We predicted that with 16.9% growth in the overall population and dramatic aging with these 2 urban centers, the burdens of cancer incidence will increase sharply in both cities over the next decades. Data on projections of cancer incidence in both cities provide useful insights for directing appropriate policies and cancer control programs in Vietnam.


Subject(s)
Forecasting , Neoplasms/epidemiology , Population Dynamics/trends , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Aging , Child , Child, Preschool , Cities/epidemiology , Cities/statistics & numerical data , Female , Humans , Incidence , Infant , Infant, Newborn , Linear Models , Male , Middle Aged , Registries/statistics & numerical data , Risk Factors , Vietnam/epidemiology , Young Adult
6.
Int J Dermatol ; 58(3): 279-282, 2019 Mar.
Article in English | MEDLINE | ID: mdl-29873062

ABSTRACT

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with a growing health concern, because of its high prevalence and associated low quality of life. The etiology of AD is multifactorial with interaction between various factors such as genetic predisposition, immune, and importantly, environmental factors. Since climate change is associated with a profound shift in environmental factors, we suggest that AD is being influenced by climate change. This review highlights the effects of ultraviolet light, temperature, humidity, pollens, air pollutants, and their interaction between them contributing to the epidemiology and pathophysiology of AD.


Subject(s)
Climate Change , Dermatitis, Atopic/epidemiology , Dermatitis, Atopic/etiology , Air Pollutants/adverse effects , Humans , Humidity , Pollen/adverse effects , Prevalence , Severity of Illness Index , Temperature , Ultraviolet Rays/adverse effects
8.
Am J Dermatopathol ; 40(3): 185-190, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29470304

ABSTRACT

Central nervous system involvement by mycosis fungoides (MF) is rare and is usually seen in advanced stages of the disease. We describe a patient with early-stage follicular MF who presented with changes in mental status. Despite an initial diagnosis of vasculitis based on clinical and brain biopsy results, the postmortem examination revealed extensive infiltration of MF cells throughout the brain with leptomeningeal involvement. This case in addition to the accompanied review of literature illustrates the importance of the awareness of central nervous system involvement by MF and highlights the need for an urgent neurologic evaluation in patients with a history of MF now presenting with neurologic signs or symptoms.


Subject(s)
Brain Neoplasms/pathology , Mycosis Fungoides/pathology , Skin Neoplasms/pathology , Fatal Outcome , Humans , Male , Middle Aged
11.
Case Rep Pathol ; 2017: 8257590, 2017.
Article in English | MEDLINE | ID: mdl-28584672

ABSTRACT

Keratoacanthoma (KA) is a benign epithelial tumor that typically presents as a firm, cone-shaped, flesh-colored nodule with a central horn-filled crater. KA is considered to be a low-grade variant of squamous cell carcinoma (SCC). We report a rare case of a 72-year-old male who presented with a KA involving the nasal septum, possibly related to ranibizumab use. A flesh-colored lesion on the right anterior nasal septum lesion was visualized on examination. Histologic examination revealed a well-circumscribed, dome-shaped central crater filled with keratin, well-differentiated squamous epithelium with ground-glass cytoplasm with pushing margins, and intraepithelial microabscesses establishing the diagnosis of KA. KA of the nasal septum has only been reported once in the literature. This case is unusual because it normally presents on sun-exposed areas. Additionally, this patient was taking ranibizumab, a vascular endothelial growth factor (VEGF) inhibitor for macular degeneration. Despite ranibizumab not being directly linked to precancerous and cancerous skin lesions, agents in this medication class have been. Although it is difficult to prove associations in this isolated case, the role of ranibizumab causing cutaneous lesions should be further investigated.

12.
Ann Diagn Pathol ; 28: 54-59, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28648940

ABSTRACT

BACKGROUND: Negative immunoregulatory checkpoints impede effective immune responses to tumor and reduce the action of anticancer agents. One such example is programmed death marker-1 (PD-1), an inhibitory signaling receptor expressed on activated and regulatory T-cells. PD-1 expression was reported in a few reports, but the expression profile of PD-1 and mycosis fungoides (MF) remains largely to be characterized. DESIGN: In this study, skin biopsies from 42 prelymphomatous T-cell dyscrasias (CLD), 9 Sezary's syndrome (SS), 103 MF, and 20 CD30+ lymphoproliferative diseases (LPD) were examined for PD-1 expression using immunohistochemistry. RESULTS: PD-1 staining was observed amidst many neoplastic T-cells in 6/9(66.7%) and 62/103 (60.2%) cases of SS and MF respectively, while only 6/42 (14.3%) cases of CLD and 0/20 (0%) cases of CD30+ LPD (P<0.001). Three cases are from same patients representing different stages of disease evolution from CLD to MF and SS with a corresponding enrichment of PD-1 positivity. In all cases there was variable staining of PD-1 amidst macrophages. There was no correlation with disease progression among MF cases. Twenty cases of CD30+ LPD did not show any PD-1 positivity. CONCLUSION: PD-1 seems to correlate with disease progression in epitheliotropic T cell dyscrasias ranging from minimal staining in prelymphomatous dyscrasias to significant staining in MF, likely reflecting the effects of PD-1 on inhibiting tumor surveillance regulatory T cell populations. PD-1 was consistently expressed in MF while it was consistently negative in primary CD30+ LPD, suggesting the possibility of using PD-1 as a means of distinguishing CD30+ MF from primary cutaneous ALCL.


Subject(s)
Lymphoma, T-Cell, Cutaneous/metabolism , Mycosis Fungoides/metabolism , Programmed Cell Death 1 Receptor/metabolism , Sezary Syndrome/metabolism , Skin Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Diagnosis, Differential , Female , Humans , Immunohistochemistry/methods , Ki-1 Antigen/metabolism , Lymphoma, T-Cell, Cutaneous/pathology , Male , Middle Aged , Mycosis Fungoides/pathology , Sezary Syndrome/pathology , Skin/pathology , Skin Neoplasms/pathology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Up-Regulation
13.
Am J Dermatopathol ; 39(5): 374-383, 2017 May.
Article in English | MEDLINE | ID: mdl-28375859

ABSTRACT

Primary cutaneous follicular helper T-cell (Tfh) lymphoma is a recently described variant of peripheral T-cell lymphoma-not otherwise specified. This particular variant, usually presenting as a sudden onset of multiple plaques and nodules, is characterized by tumoral atypical T cells that express an array of Tfh markers, such as inducible T-cell costimulator, Bcl-6, CXCL13, PD-1, and CD10. The authors now present 3 patients whose known clinical skin findings are consistent with PTCL of Tfh origin (PTCL-Tfh). The typically protracted pattern of skin disease manifesting as scaly patches and plaques encountered in mycosis fungoides was not seen in our 3 cases, and there were distinguishing light microscopic and phenotypic features. These cases are similar to the few previous reported cases of PTCL-Tfh, although systemic involvement was not seen. The categorization of additional patients into this PTCL subtype in the medical literature would be needed to further characterize this new entity and may lead to better targeted treatments based on specific T-cell subtypes.


Subject(s)
Lymphoma, T-Cell, Cutaneous/pathology , Lymphoma, T-Cell, Cutaneous/therapy , Skin Neoplasms/pathology , Skin Neoplasms/therapy , T-Lymphocytes, Helper-Inducer/pathology , Aged , Biopsy, Needle , Combined Modality Therapy , Dermatologic Surgical Procedures/methods , Follow-Up Studies , Humans , Immunohistochemistry , Male , Methotrexate/therapeutic use , Middle Aged , Rare Diseases , Risk Assessment , Treatment Outcome , Young Adult
15.
Dermatol Online J ; 23(11)2017 Nov 15.
Article in English | MEDLINE | ID: mdl-29447634

ABSTRACT

BACKGROUND: Lymphomatoid drug reactions can mimic endogenous T and B cell lymphoproliferative diseases. OBJECTIVES: We present a novel form of cutaneous drug reaction with features of pityriasis lichenoides (PL), a recognized form of T cell dyscrasia. METHODS: Ten cases were studied where a cutaneous eruption exhibiting semblance to PL within a few weeks to months after starting a particular drug. RESULTS: The patient cohort comprised 7 females and 3 males with the mean age of 60 years. Widely distributederythematous cutaneous lesions were present in 6 cases whereas a more localized distribution was seen in three cases. The most frequently implicated drugsassociated with the eruption were antidepressants and statins. Histologic examination showed a morphologic picture identical to PL including marked epitheliotropism of mildly atypical lymphocytes, psoriasiform epidermal hyperplasia, dyskeratosis, hemorrhage, and a thick parakeratotic scale. Therewas a significant reduction in the expression of CD7 and CD62L amid the T cells. Regression of the eruption occurred in all cases excluding one. CONCLUSION: Thefindings conform the categorization of this process as a form of T-cell dyscrasia albeit one that is reversible, dependent on the drug withdrawal. The limitationof our study includes the retrospective design of the study.


Subject(s)
Drug Eruptions/pathology , Lichenoid Eruptions/chemically induced , Pityriasis Lichenoides/pathology , Skin/pathology , Adult , Aged , Aged, 80 and over , Antidepressive Agents/adverse effects , Diagnosis, Differential , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Lichenoid Eruptions/pathology , Male , Middle Aged , Retrospective Studies , T-Lymphocytes/immunology
16.
Am J Dermatopathol ; 39(7): 508-517, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27655118

ABSTRACT

INTRODUCTION: Lymphomatoid drug reactions are atypical T cell cutaneous lymphocytic infiltrates induced by pharmacological therapy. Due to phenotypic abnormalities, clonality, and their close clinical and morphologic resemblance to T cell lymphomas, these eruptions have been categorized as drug-associated reversible granulomatous T cell dyscrasias. DESIGN: A total of 20 cases were encountered in which a diagnosis of CD30 lymphomatoid drug reaction was rendered. RESULTS: There were 11 women and 9 men ranging from 31 to 86 years of age presenting with a sudden onset often generalized cutaneous papular eruption. Two patients had vasculitic lesions. In all cases, a positive drug history was elicited and in most the initiation of the drug was temporally associated with the cutaneous eruption. Among the implicated drugs were statins (6 cases), immunomodulators (4 cases), ACE inhibitors (3 cases), antibiotics (3 cases), chemotherapy agents (3 cases), and antidepressants (1 case). Biopsies demonstrated a similar morphology, namely a superficial angiocentric lymphocytic infiltrate containing many immunoblasts. Tissue eosinophilia, interface dermatitis, and supervening eczematous changes in the overlying epidermis were observed in most cases. In all cases, the angiocentric infiltrate was highlighted by CD3, CD30, and CD4. Cytotoxic protein granule expression or monoclonality was not observed. In all cases, there was improvement or complete regression of the eruption upon drug modulation. CONCLUSION: The CD30 positive lymphomatoid angiocentric drug reaction poses a diagnostic challenge because of its close resemblance to type A lymphomatoid papulosis and potential confusion with a peripheral T cell lymphoma with large cell transformation.


Subject(s)
Biomarkers, Tumor/analysis , Drug Eruptions/diagnosis , Drug Eruptions/pathology , Ki-1 Antigen/analysis , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphomatoid Papulosis/diagnosis , Male , Middle Aged , Skin Neoplasms/diagnosis
17.
Am J Dermatopathol ; 39(1): 28-32, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27759688

ABSTRACT

Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities. Histopathologic examination of the hand biopsy revealed coalescing nodules of large atypical noncerebriform lymphocytes with focal areas of epidermotropism. Phenotypically, the infiltrate was positive for ß-F1, CD2, CD4, CD5, CD7, Foxp3, and CD25. In both biopsies, there was striking upregulation of TOX (thymocyte selection-associated high mobility group box factor) in the nuclei of neoplastic cells. The second biopsy taken from the ichthyotic patch on the patient's left leg showed a subtle pattern of epidermal infiltration by atypical noncerebriform lymphocytes and a distinct compact scale consistent with the clinical picture of ichthyosis. The histopathologic appearance was that of a yet undescribed ichthyosiform mycosis fungoides-like presentation of chronic ATLL. In addition, the observed upregulation of nuclear TOX may play an oncogenic role in ATLL. The course to date in this patient has been relatively indolent, although the patients believe that large cell transformation could portend more aggressive disease.


Subject(s)
Biomarkers, Tumor/analysis , High Mobility Group Proteins/analysis , Ichthyosis/metabolism , Leukemia-Lymphoma, Adult T-Cell/metabolism , Mycosis Fungoides/chemistry , Skin Neoplasms/chemistry , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Female , Humans , Ichthyosis/drug therapy , Ichthyosis/pathology , Immunohistochemistry , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Leukemia-Lymphoma, Adult T-Cell/pathology , Mycosis Fungoides/drug therapy , Mycosis Fungoides/pathology , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Treatment Outcome , Up-Regulation
18.
Indian J Dermatol Venereol Leprol ; 82(4): 395-403, 2016.
Article in English | MEDLINE | ID: mdl-27279297

ABSTRACT

BACKGROUND: Atypical epitheliotropic T cell lymphocytic infiltrates are commonly encountered in routine and consultative dermatopathology practices and typically do not represent mycosis fungoides. Other conditions can mimic certain light microscopic and phenotypic findings encountered in mycosis fungoides, comprising a diverse spectrum of conditions including the lymphomatoid drug reaction, collagen vascular disease, viral hypersensitivity reactions and cutaneous T cell dyscrasia. AIMS: To examine biopsies obtained from cutaneous T cell dyscrasia localized to the palms and soles and to evaluate whether it exhibits a morphologic and pathogenetic continuum with mycosis fungoides plantaris et palmaris. METHODS: We examined 13 biopsies showing an epidermotropic superficial lymphocytic infiltrate from thirteen patients who presented with a palmar and/or plantar keratoderma without other sites of cutaneous involvement. Conventional light microscopy, immunophenotyping and clonality studies were carried out. The clinical features were recorded. RESULTS: Biopsies showed a variably dense, superficial, angiocentric CD4 or CD8 dominant lymphocytic infiltrate accompanied by a non-destructive pattern of epidermotropism. Low-grade cerebriform atypia along with variable diminution in the expression of CD7 and CD62L was noted. In three cases, statins were suspected to be the cause. Due to lack of familiarity with the entity, treatment interventions were inconsistent and not aggressively pursued. There was no evidence of disease progression to mycosis fungoides in any case. LIMITATIONS: The limitations of this study include the lack of long-term follow up and information on the nature of the therapeutic interventions and responses to treatment. CONCLUSION: The spectrum of cutaneous lymphoid dyscrasias should be expanded to include cases manifesting as palmo-plantar keratoderma. These cases are to be distinguished from mycosis fungoides palmaris et plantaris. As with other forms of cutaneous lymphoid dyscrasia, the lesions tend to be persistent. The course however, is indolent in most cases.


Subject(s)
Keratoderma, Palmoplantar/diagnosis , Mycosis Fungoides/diagnosis , Paraproteinemias/diagnosis , Skin Neoplasms/diagnosis , T-Lymphocytes/pathology , Adult , Aged , Child , Diagnosis, Differential , Female , Humans , Keratoderma, Palmoplantar/immunology , Male , Middle Aged , Mycosis Fungoides/immunology , Paraproteinemias/immunology , Skin Neoplasms/immunology , T-Lymphocytes/immunology
19.
Mol Cell Biochem ; 416(1-2): 63-70, 2016 May.
Article in English | MEDLINE | ID: mdl-27048505

ABSTRACT

Atopic dermatitis is a chronic inflammatory skin disease characterized by the dysregulation of the epidermal barrier and the immune system. Interleukin (IL)-13, a key T helper 2 cytokine, has been shown to impair the epidermal barrier function via downregulating epidermal barrier proteins. MicroRNAs are small noncoding RNAs of approximately 22 nucleotides that act as negative regulators of gene expression at posttranscriptional levels. MicroRNA-143 is known to be a tumor suppressor in various tumors; however, its role in the regulation of allergic diseases including atopic dermatitis remains elusive. In this study, we investigated whether IL-13Rα1 was a microRNA-143 target to regulate the effects of IL-13 on epidermal barrier function. After the stimulation of IL-13 in human epidermal keratinocytes, the level of microRNA-143 was decreased. The luciferase activity of the vector containing 3'UTR of IL-13Rα1 was decreased in keratinocytes transfected with microRNA-143 mimic compared to those of the corresponding controls. The forced expression of microRNA-143 mimic blocked the IL-13-induced downregulation of filaggrin, loricrin, and involucrin in epidermal keratinocytes. Collectively, these data suggest that microRNA-143 suppresses IL-13 activity and inflammation through targeting of IL-13Rα1 in epidermal keratinocytes. MicroRNA-143 may serve as a potential preventive and therapeutic target in atopic dermatitis.


Subject(s)
Dermatitis, Atopic/metabolism , Epidermis/metabolism , Interleukin-13 Receptor alpha1 Subunit/biosynthesis , Interleukin-13/biosynthesis , Keratinocytes/metabolism , MicroRNAs/biosynthesis , Cells, Cultured , Dermatitis, Atopic/genetics , Dermatitis, Atopic/pathology , Epidermis/pathology , Filaggrin Proteins , Humans , Interleukin-13/genetics , Interleukin-13 Receptor alpha1 Subunit/genetics , Intermediate Filament Proteins/biosynthesis , Intermediate Filament Proteins/genetics , Keratinocytes/pathology , Membrane Proteins/biosynthesis , Membrane Proteins/genetics , MicroRNAs/genetics , Protein Precursors/biosynthesis , Protein Precursors/genetics
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