Topical administration of EGF suppresses immune response and protects skin barrier in DNCB-induced atopic dermatitis in NC/Nga mice

Kim, Young-Je; Choi, Mi Ji; Bak, Dong‐Ho; Lee, Byung Chul; Ko, Eun Jung; Ahn, Ga Ram; Ahn, Seungjoon; Kim, Moo Joong; Na, Jungtae; Kim, Beom Joon

doi:10.1038/s41598-018-30404-x

Cited by 61 publications

(76 citation statements)

References 61 publications

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“…Recently, it has been shown that topical administration of EGF suppresses immune response and protects skin barrier in DNCB‐induced ADin NC/Nga mice. This effect appeared to be the result of EGF upregulation of epidermal proteins and downregulation of TSLP (thymic stromal lymphopoietin)‐mediated mast cell and Th2 cell activation . Therefore, we propose that in subsets of patients with EGF deficiency, replacement therapy with topical or systemically administered EGF may be of clinical value.…”

Section: Discussionmentioning

confidence: 94%

Quantitative profiling of cytokines and chemokines in DOCK8‐deficient and atopic dermatitis patients

Jacob

Khalaf

Alhissi

et al. 2018

Allergy

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Background: Hyper-IgE syndromes (HIES) are a clinically overlapping, heterogeneous group of inborn errors of immunity characterized by elevated serum IgE level, eosinophilia, atopy, and immune dysregulation. Deficiency of DOCK8 protein is potentially a life-threatening autosomal recessive HIES and only curable with bone marrow transplantation. Hence, the diagnosis of DOCK8 deficiency is critical and should be sought at an early stage to initiate definitive therapy.Methods: Serum samples from patients with DOCK8 deficiency and atopic dermatitis were profiled on a cytokine/chemokine panel for potential differential expression.Results: CXCL10 and TNF-A were upregulated in DOCK8 patients when compared to AD, possibly contributing toward increased susceptibility to infections and cancer.In contrast, epidermal growth factor (EGF) was significantly downregulated in a subgroup of DOCK8-deficient and AD patients, while IL-31 expression was comparable between both DOCK8-deficient and AD cohorts, possibly contributing toward pruritus seen in both groups.Conclusion: This comprehensive cytokine profile in HIES patients reveals distinctive biomarkers that differentiate between the DOCK8-deficient and AD patients. The unique expression profile of various inflammatory cytokines in patients with DOCK8 deficiency vs atopic dermatitis likely reflects disease-specific perturbations in multiple cellular processes and pathways leading to a predisposition to infections and allergies seen in these patients. These data agree with the role for EGF replacement therapy in EGF-deficient individuals with AD as well as DOCK8 deficiency through a potential shared pathway. In addition, these novel biomarkers may be potentially useful in distinguishing DOCK8 deficiency from AD allowing early-targeted treatment options. K E Y W O R D S atopic dermatitis, CXCL10, DOCK8, epidermal growth factor, hyper-IgE syndrome Abbreviations: EGF, epidermal growth factor; EPAS1, endothelial PAS domain protein 1; GCSF, CSF3 is colony-stimulating factor3; HIES, hyper-IgE syndrome; IL-31, interleukin-31; MDC, macrophage-derived chemokine; OPLS-DA, orthogonal projections to latent structures discriminant analysis; PGM3, phosphoglucomutase 3; STAT3, signal transducer activator of transcription 3; TNF, tumor necrosis factor.

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Section: Discussionmentioning

confidence: 94%

Quantitative profiling of cytokines and chemokines in DOCK8‐deficient and atopic dermatitis patients

Jacob

Khalaf

Alhissi

et al. 2018

Allergy

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“…These findings supported that sustaining a close to normal kidney function is an integral component of the tolerized phenotype. Several genes involved in immune regulation, such as Egf ( 34 ) and S100g ( 35 ), also showed significantly heightened expression in kidney cells from tolerized and naive kidneys in comparison with those from rejecting kidneys ( Supplemental Figure 2B ). In contrast, the expression of chemokine genes such as Ccl5 and Ccl8 was significantly enhanced in kidney cells from rejecting kidneys in comparison with those from tolerized or naive kidneys ( Supplemental Figure 2C ).…”

Section: Resultsmentioning

confidence: 99%

Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection

Dangi¹,

Natesh²,

Husain³

et al. 2020

JCI Insight

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Myeloid cells are increasingly recognized as major players in transplant rejection. Here, we used a murine kidney transplantation model and single cell transcriptomics to dissect the contribution of myeloid cell subsets and their potential signaling pathways to kidney transplant rejection. Using a variety of bioinformatic techniques, including machine learning, we demonstrate that kidney allograft–infiltrating myeloid cells followed a trajectory of differentiation from monocytes to proinflammatory macrophages, and they exhibited distinct interactions with kidney allograft parenchymal cells. While this process correlated with a unique pattern of myeloid cell transcripts, a top gene identified was Axl , a member of the receptor tyrosine kinase family Tyro3/Axl/Mertk (TAM). Using kidney transplant recipients with Axl gene deficiency, we further demonstrate that Axl augmented intragraft differentiation of proinflammatory macrophages, likely via its effect on the transcription factor Cebpb. This, in turn, promoted intragraft recruitment, differentiation, and proliferation of donor-specific T cells, and it enhanced early allograft inflammation evidenced by histology. We conclude that myeloid cell Axl expression identified by single cell transcriptomics of kidney allografts in our study plays a major role in promoting intragraft myeloid cell and T cell differentiation, and it presents a potentially novel therapeutic target for controlling kidney allograft rejection and improving kidney allograft survival.

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“…Immunoreactivities of TNF-α, interleukins and HMGB1 were analyzed from the 7 sections per mouse according to a published protocol [ 26 ] with modification. Their images were taken in the tissue area of 70 μm 2 of the dorsal skin using an AxioM1 light microscope (Carl Zeiss, Oberkochen, Germany) equipped with a digital camera (DP72) (Olympus, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…To examine the expression levels of TNF-α, IL-1β, IL-4 and IL-13, western blot analyses were carried out in accordance to our previous study with modification [26]. Briefly, seven animals per group were sacrificed under deep anesthesia by intraperitoneal injection of pentobarbital sodium (60 mg/kg) (JW Pharm.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Effects of Decursin and Angelica gigas Nakai Root Extract on Hair Growth in Mouse Dorsal Skin via Regulating Inflammatory Cytokines

Lee

Kim

et al. 2020

Molecules

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This current study investigates the facilitative effects and mechanisms of decursin, a major component of Angelica gigas Nakai (AGN), and AGN root extract on hair growth in mice. We perform high-performance liquid chromatography on AGN extract to show it contains 7.3% decursin. Hairs in mouse dorsal skin are shaved distilled in water, 0.15% decursin, and 2% AGN root extract (0.15% decursin in the diluted extract) and topically applied twice a day for 17 days. Hematoxylin and eosin staining are done to examine the morphological changes in the hair follicles. To compare the effects of decursin and AGN extract on inflammatory cytokines in the dorsal skin, Western blot analysis and immunohistochemistry for tumor necrosis factor α (TNF-α) and interleukin (IL)-1β as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines are conducted. The results show that the application of decursin and AGN extract confer effects on hair growth. Hair growth is significantly facilitated from seven days after the treatments compared to that in the control group, and completely grown hair was found 17 days after the treatments. The protein levels and immunoreactivity of TNF-α and IL-1β in this case are significantly decreased, whereas the IL-4 and IL-13 levels and immunoreactivity are significantly increased compared to those in the control group. Additionally, high-mobility group box 1, an inflammatory mediator, is elevated by the topical application of decursin and AGN extract. Taken together, the treatment of mouse dorsal skin with AGE root extract containing decursin promotes hair growth by regulating pro- and/or anti-inflammatory cytokines. We, therefore, suggest that AGN root extract as well as decursin can be utilized as materials for developing hair growth-facilitating treatments.

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Topical administration of EGF suppresses immune response and protects skin barrier in DNCB-induced atopic dermatitis in NC/Nga mice

Cited by 61 publications

References 61 publications

Quantitative profiling of cytokines and chemokines in DOCK8‐deficient and atopic dermatitis patients

Quantitative profiling of cytokines and chemokines in DOCK8‐deficient and atopic dermatitis patients

Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection

Effects of Decursin and Angelica gigas Nakai Root Extract on Hair Growth in Mouse Dorsal Skin via Regulating Inflammatory Cytokines

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