Expression of Elafin in Dermatitis Herpetiformis

Ollague, Jose E.; Nousari, Carlos H.

doi:10.1097/dad.0000000000000915

Cited by 7 publications

(4 citation statements)

References 14 publications

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“…In our previous studies, we found that the oral traditional Chinese medicine, YinXieLing, exerts its therapeutic effect on psoriasis by inhibiting of cell proliferation and pro-inflammation while increasing CD4+ Foxp3+ regulatory t cell generation 39-41. These results align well with previous studies that show that PI3 downregulates neutrophil-mediated inflammation and IFNG inhibits neutrophil accumulation 56-59.…”

Section: Discussionsupporting

confidence: 89%

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine

Xu¹,

Deng²,

Xu³

et al. 2019

Theranostics

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Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. Methods : To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. Results : Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). Conclusion : Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases.

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Section: Discussionsupporting

confidence: 89%

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine

Xu¹,

Deng²,

Xu³

et al. 2019

Theranostics

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“…A recent study demonstrated a down-regulation of elafin, a serine protease inhibitor that inhibits a neutrophil mediated inflammatory response, in keratinocytes from DH skin. A similar finding could be also found in the epithelial cells from the small bowel of patients with active CD (124).…”

Section: Pathogenesissupporting

confidence: 79%

Dermatitis Herpetiformis: Novel Perspectives

et al. 2019

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Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.

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“…Furthermore, PI3, FOSL1 and CXCL1 were each found to interact with CXCL8 following the construction of the protein interaction network of the four genes. The PI3 gene is a serine protease inhibitor that can inhibit excessive damage to elastase released by neutrophils during the inflammation process to resist the inflammatory response, antiviral and immunomodulatory effects (26)(27)(28)(29)(30). It has been previously reported that PI3 levels are increased in the blood of children with AD (31).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential miR‑155 target genes in epidermal immune microenvironment of atopic dermatitis patients and their inflammatory effects on HaCaT cells

Wang,

Chen,

Chen

et al. 2023

Exp Ther Med

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Atopic dermatitis (AD) is a common inflammatory skin condition and the leading cause of morbidity associated with skin conditions worldwide. For the majority of patients, AD is a lifelong disease that cannot be cured completely. Therefore, in the present study, differentially expressed genes (DEGs) in the epidermal immune microenvironment were screened using bioinformatic techniques. Subsequently, an in vitro cellular model was constructed to investigate the role of microRNA (miR)-155 in immune infiltration during AD. In the present study, two datasets (GSE121212 and GSE157194) were downloaded from Gene Expression Omnibus, before the DEGs were screened and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses. miRNet was used to predict the possible target genes of miR-155 among the differentially expressed genes found. Consequently, peptidase inhibitor 3 (PI3), FOS-like 1, AP-1 transcription factor subunit (FOSL1), C-X-C motif chemokine ligand (CXCL)1 and CXCL8 were selected to be the potential target genes of miR-155 in the epidermal immune microenvironment of patients with AD. Concurrently, an inflammatory cell model using HaCaT cells was constructed by TNF-α and IFN-γ treatment. The effects of miR-155 on HaCaT cell proliferation and secretion of IL-1β, IL-6, IL-10, IL-15, PI3, FOSL1, CXCL1 and CXCL8 under inflammatory and non-inflammatory conditions were then analyzed. The results showed that after the HaCaT cells were transfected with miR-155, miR-155 inhibited HaCaT cell proliferation and decreased the mRNA expression levels of PI3 and CXCL8, increased the mRNA levels of FOSL1 and secretion levels of IL-1β, IL-6, IL-15 and CXCL1. By contrast, miR-155 decreased the secretion levels of IL-10 and CXCL8. In the inflammatory cell model of HaCaT cells, miR-155 was found to significantly inhibit the proliferation of HaCaT cells during inflammation whilst significantly increasing the secretion of IL-1β, IL-6, IL-10 and IL-15. In addition, miR-155 increased the mRNA expression and secretion levels of CXCL1 and CXCL8, whilst also increasing the mRNA expression levels of PI3. Results from the current study suggest that miR-155 can stimulate keratinocytes to produce inflammatory cytokines and proteins to enhance the inflammatory response in AD.

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Expression of Elafin in Dermatitis Herpetiformis

Cited by 7 publications

References 14 publications

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine

Dermatitis Herpetiformis: Novel Perspectives

Identification of potential miR‑155 target genes in epidermal immune microenvironment of atopic dermatitis patients and their inflammatory effects on HaCaT cells

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