- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis, Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Preclinical, Journal: CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis. (Pubmed Central) - Jul 7, 2023
We proved that CKBA suppressed mast cell activation via ERK signaling using the ERK activator (t-butyl hydroquinone) and inhibitor (selumetinib; AZD6244) in AD. Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Morphea Linier (En Coup De Sabre) In A 21 Year-Old Woman () - Jul 3, 2023 - Abstract #WCD2023WCD_7039;
Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD. The patient had administered Daivonex
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Discovering and controlling immunopathogenic mediators inducing allergic itching () - Jul 3, 2023 - Abstract #WCD2023WCD_4239;
We applied calcipotriol (MC903), a low-calcium analog of vitamin D3, and ovalbumin (OVA) allergen on the ears of mice to induce pruritus associated with allergic inflammatory changes...The datasets of transcriptomic analysis of patients with atopic dermatitis found on the Gene Expression Omnibus revealed an increase of the specific gens observed in the mice skin lesion. In summary, our findings suggest that targeting immunopathogenic mediators could be a promising therapeutic strategy for the management of pruritus
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
TET2 affect epidermal barrier homeostasis and regulates type 2 inflammation in atopic dermatitis () - Jul 3, 2023 - Abstract #WCD2023WCD_3870;
MATERIALS AND To explore the role of epidermal TET2 in AD pathogenic mechanisms, we collected tissues from AD patients and constructed MC903-AD mouse model using TET CKO (K14cre; TET2flox/flox) mice... Our study showed that epidermal TET2 is involved in the regulation the epidermal barrier homeostasis and influenced the release of type 2 cytokines in AD, which highlight the role of epigenetic regulation in AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Mast cell MRGPRX2/MrgprB2 activation promotes inflammation reaction in atopic dermatitis () - Jul 3, 2023 - Abstract #WCD2023WCD_3861;
MATERIALS AND Wild type (WT) and MrgprB2 knockout (MrgprB2-/-) mice were used to construct calcipotriol (MC903) AD mouse model, and H&E staining, immunofluorescent staining were used to show pathological changes and MCs activation... Our study clarified that MRGPRX2-mediated MC activation promotes AD inflammatory reaction by release tryptase.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Application of low-level laser with 1064nm Q-switched Nd: YAG laser may ameliorate atopic dermatitis (Poster Zone A) - May 13, 2023 - Abstract #EAACI2023EAACI_2235;
Method Experimental AD mouse model triggered by topical application of MC903 was employed...Conclusion 1064-nm QS laser with the energy under LLLT ameliorates AD skin lesions and itch by inhibiting Th2 responses. 1064-nm QS laser can be considered a potential therapeutic choice for AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Diminished ?? T Cells during allergic skin inflammation is mediated by IL-4 signaling in keratinocytes (P411) (Exhibit Hall; Poster Board No. P411) - Apr 11, 2023 - Abstract #IMMUNOLOGY2023IMMUNOLOGY_1033;
Our previous work identified a loss of DETC in Stat6VT mice and in MC903 induced skin inflammation mouse model that was dependent on IL-4...Together, these results identify an IL-4-dependent circuit that regulates DETCs in the skin by repressing IL-15 expression in keratinocytes. This provides further insights into the ability of IL-4 to promote the development of atopic lesions and impair wound healing.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
The roles of epidermal Blimp-1 in atopic dermatitis (P507) (Exhibit Hall; Poster Board No. P507) - Apr 11, 2023 - Abstract #IMMUNOLOGY2023IMMUNOLOGY_889;
Since K5-CreER+ Prdm1f/f (CKO) mice in Balb/c background exhibited AD-like symptoms, we wondered whether they are more susceptible to the disease progression in a murine AD model induced by MC903, a vitamin D3 analog enhancing TSLP production by keratinocytes...Indeed, both in vivo and in vitro deletion of Prdm1 in keratinocytes resulted in elevated levels of ERV transcripts. We are studying the contribution of elevated ERV transcripts in Blimp-1-reduction-mediated AD-like skin inflammation.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Lecture 6: Molecular insight of topical emollient on the development of atopic dermatitis and atopic march in a mice model: Q&A (Harmony, 44F Keio Plaza Hotel, Tokyo) - Apr 5, 2023 - Abstract #ISID2023ISID_1890;
Following induction of atopic dermatitis with topical calcipotriol (MC903) and ovalbumin (OVA), one group of mice was treated topically with a linoleic acid-ceramide-containing emollient, while mice without emollient treatment served as controls...In conclusion, Topical emollient not only reduces skin inflammation, but also mitigates systemic inflammation by decreasing TSLP and IgE levels. Moreover, topical emollient reduces chemokine production, and basophil infiltration and activation in the lung, providing a molecular basis for blocking the atopic march.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Lecture 6: Molecular insight of topical emollient on the development of atopic dermatitis and atopic march in a mice model: Presentation (Harmony, 44F Keio Plaza Hotel, Tokyo) - Apr 5, 2023 - Abstract #ISID2023ISID_1889;
Following induction of atopic dermatitis with topical calcipotriol (MC903) and ovalbumin (OVA), one group of mice was treated topically with a linoleic acid-ceramide-containing emollient, while mice without emollient treatment served as controls...In conclusion, Topical emollient not only reduces skin inflammation, but also mitigates systemic inflammation by decreasing TSLP and IgE levels. Moreover, topical emollient reduces chemokine production, and basophil infiltration and activation in the lung, providing a molecular basis for blocking the atopic march.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Mouse Models for Atopic Dermatitis. (Pubmed Central) - Mar 28, 2023
This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Application of MC903 and gross phenotype assessment Basic Protocol 2: Processing skin for flow cytometry analysis Support Protocol: Skin immune cell surface staining and flow cytometry analysis Basic Protocol 3: Harvesting skin for histologic analysis Basic Protocol 4: Immunofluorescence staining to identify immune cell infiltrates.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis, adriforant (ZPL 3893787) / Novartis
Preclinical, Journal: Adriforant is a functional antagonist of histamine receptor 4 and attenuates itch and skin inflammation in mice. (Pubmed Central) - Mar 21, 2023
The effects observed in mice, however, did not translate to clinical efficacy in patients as the Ph2b clinical trial with adriforant did not meet pre-specified efficacy endpoints. Given the complex pathogenesis of AD, antagonism of histamine receptor 4 alone appears insufficient to reduce disease severity in AD patients, despite the effects seen in mouse models.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: A Mouse Model of MC903-Induced Atopic Dermatitis. (Pubmed Central) - Mar 14, 2023
Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Topical application of MC903 induces AD-like skin inflammation Support Protocol 1: Measurement of ear skin thickness Support Protocol 2: Itch assessment Support Protocol 3: Dissection of ear skin and ear draining lymph nodes Support Protocol 4: Histological evaluation and quantification Support Protocol 5: Preparation of single-cell suspension from ear skin and draining lymph nodes for the assessment of inflammatory immune cell infiltration using flow cytometry.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: IL-31-generating network in atopic dermatitis comprising macrophages, basophils, thymic stromal lymphopoietin, and periostin. (Pubmed Central) - Mar 7, 2023
Basic Protocol: Topical application of MC903 induces AD-like skin inflammation Support Protocol 1: Measurement of ear skin thickness Support Protocol 2: Itch assessment Support Protocol 3: Dissection of ear skin and ear draining lymph nodes Support Protocol 4: Histological evaluation and quantification Support Protocol 5: Preparation of single-cell suspension from ear skin and draining lymph nodes for the assessment of inflammatory immune cell infiltration using flow cytometry. A network comprising IL-31-expressing macrophages, TSLP, periostin, and basophils plays a significant role in AD itch.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Elevation of TARC by anti-IL-31 receptor antibody in a murine atopic dermatitis model () - Mar 4, 2023 - Abstract #ISID2023ISID_1342;
To clarify this mechanism, using a calcipotriol (MC903)-induced AD mouse model, we found increased expression of IL-31 in the skin and increased levels of TARC in the serum...Taken together, we demonstrated the increase level of TARC in the serum and skin with anti-IL-31RA treatment in a murine AD model. Further study is needed to identify the TARC-producing dermal cells, such as dendritic cells, macrophages, fibroblasts, and endothelial cells, during anti-IL-31RA antibody treatment.
- |||||||||| Eucrisa (crisaborole) / Pfizer
Crisaborole inhibits itch and pain by preventing neutrophil infiltration () - Mar 4, 2023 - Abstract #ISID2023ISID_1334;
Additionally, using the cheek skin injection model, we found that S100A8/A9 enhanced not only itch-related behaviors evoked by histamine or chloroquine, but also pain-related behaviors. These findings suggest that the PDE-4 inhibitor reduces itch and pain in atopic dermatitis, in part by inhibiting infiltration of S100A8/9-containing neutrophils.
- |||||||||| Zyclara (imiquimod) / Mochida, Viatris, Bausch Health, Dovonex (calcipotriol) / LEO Pharma, Novartis
Epidermis-intrinsic N6-methyladenosine modification dampens skin inflammation () - Mar 4, 2023 - Abstract #ISID2023ISID_1265;
The results of MeRIP-seq suggested that reprogramming of fatty acid metabolism in KCs might play an important role in the maintenance of skin immune homeostasis by METTL3. This study provides a solid foundation for further research on the effect of m 6 A modification in KCs in the pathogenesis of skin inflammation, such as psoriasis and AD.
- |||||||||| imatinib / Generic mfg.
Topical application of imatinib mesylate suppresses vitamin D3 analog-induced dermatitis in balb/c mice () - Mar 4, 2023 - Abstract #ISID2023ISID_1061;
IMT suppressed the number of infiltrating cells (CD4+ T cells, eosinophils, basophils) and the expression of IL-13, IL-33, and TSLP in a MC903-induced, murine AD model and inhibited TNF-?/IL-4-induced TSLP expression via downregulation of ERK phosphorylation in MKCs. From the results of this experiment, IMT reduced the skin symptoms in a MC903-induced, murine AD model, suggesting that it may have potential as a new treatment for AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
TRPV3 modulates mast cells biological activity via stimulating IL33 release in atopic dermatitis () - Mar 4, 2023 - Abstract #ISID2023ISID_786;
With bioinformatics investigation, we found that mast cells of TRPV3 KO mice infiltrated less in the dermis than those of wild type (WT) controls with MC903 treatment...This work expanded our understanding of TRP channels regulating itching cytokines and neuro-immunity network. More importantly, our findings provide a new theoretical basis for TRPV3 inhibitors to treat itch and inflammation in atopic dermatitis.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
The role of transient receptor potential vanilloid 4 (TRPV4) channels in atopic dermatitis () - Mar 4, 2023 - Abstract #ISID2023ISID_616;
In conclusion, we showed that TRPV4 regulates the MC903-induced atopic dermatitis-like skin inflammation via the production of TSLP and inflammation in mice. Future work will focus on immunological aspects of TRPV4 regulation in atopic dermatitis, particularly type 2 inflammation.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Fucosyltransferase 1 plays a protective role in the development of atopic dermatitis-like disease in mice (ePoster Stage 5) - Mar 4, 2023 - Abstract #ISID2023ISID_525;
Furthermore, using a MC903-induced AD-like mouse model, Fut1-deficient mice showed higher serum IgE levels, compared to WT mice...Infiltration of CD4 + T cells, Gr-1 + cells (neutrophils), and mast cells into lesion skin was significantly higher in Fut1-deficient mice than in WT mice. Thus, these findings reveal that barrier dysfunction in ?(1,2)
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Acid mantle of the stratum corneum is a shield against bacterial entry into the underlying epidermal layers (Room D (Ohgi) ) - Mar 4, 2023 - Abstract #ISID2023ISID_372;
Moreover, to investigate the microbial behavior in detail, S. aureus was inoculated to the mice with thickened SC due to topical application of MC903, which induces atopic dermatitis-like inflammation...The more basic buffer applied, the more severe skin inflammation induced. Thus, the middle acid mantle zone of the SC plays an important protective role in the invasion of pathogenic bacteria.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Propionate alleviates itch in atopic dermatitis by modulating sensory TRP channels of dorsal root ganglion (Room A (Concord Ballroom) ) - Mar 4, 2023 - Abstract #ISID2023ISID_324;
Gsdma1/a3-deficiency might be involved in AD pathogenesis, likely through GSDMA-mediated epidermal differentiation and cornification. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in vitro , attenuated MC903-induced hyper-excitability in sensory neurons, and inhibited capsaicin-evoked hTRPV1 currents (IC50=20.08
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Involucrin/ck1e/vitamin D receptor regulatory axis underlies evolution of human epidermis out of Africa (Room F (Harmony) ) - Mar 4, 2023 - Abstract #ISID2023ISID_302;
Ivl-/- mouse skin treated with MC903 (vitamin D agonist) exhibited a dampened Vdr response with notable decreased Vdr expressions in multiple scRNA-seq-identified keratinocyte populations...Together, our mouse-to-human translational studies identify a conserved Ivl/CK1e/VDR regulatory axis that underlies human skin evolution out of Africa. Our findings further highlights population-specific, molecular diversity for the human epidermis.
- |||||||||| Zyclara (imiquimod) / Mochida, Viatris, Bausch Health, Dovonex (calcipotriol) / LEO Pharma, Novartis, Xeljanz (tofacitinib) / Pfizer
Topical administration of MDI1228, a novel pan-JAK inhibitor, effectively suppresses the development of skin inflammation in mice (Room E (Moonlight) ) - Mar 4, 2023 - Abstract #ISID2023ISID_286;
Taken together, we have shown that MDI1228, a pan-JAK inhibitor, has broad spectrum inhibitory effect on activation of the immune system mediated by key cytokines including IFN?, IFN?, IL4 and/or IL17A, and as a result it effectively suppresses the development of both allergic and autoimmune skin inflammation. These results indicate that MDI1228 is a promising candidate for topical anti-inflammatory drug for various types of dermatitis.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Loss of both host-derived antimicrobial peptides and bacteriocin-producing commensals enables survival of Staphylococcus aureus on Th2-inflamed skin (Room D (Ohgi) ) - Mar 4, 2023 - Abstract #ISID2023ISID_262;
To understand why increased AMPs in AD compared to normal skin would enable increased S. aureus we analyzed the skin of Il4ra -/- or WT mice with or without MC903-induced Th2 inflammation...Notably, the selective killing of CoNS-Bac + was rescued on the skin of Camp -/- mice with Th2 inflammation. These results show that the combination of both a partial loss of host AMPs and elimination of CoNS-Bac + during Th2 inflammation can explain why S. aureus expands on AD skin.
- |||||||||| Zyclara (imiquimod) / Mochida, Viatris, Bausch Health, Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Modulation of Skin Inflammatory Responses by Aluminum Adjuvant. (Pubmed Central) - Feb 25, 2023
Together, our results suggest that the injection of a high dose of AS may inhibit Th1 and Th17 immune response-driven skin inflammation but promote type 2 immune response-driven skin inflammation. These results may provide a better understanding of how vaccination with an aluminum adjuvant alters the skin immune response to external insults.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
ILC2 activity in infants induces stronger eosinophilic skin inflammation than in adult in an atopic dermatitis mouse model. (Convention Center, Meeting Room Level, Room 206B) - Feb 4, 2023 - Abstract #AAAAI2023AAAAI_2155;
A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice. Rationale:To clarify why the pathogenesis of atopic dermatitis (AD) reportedly differs between infants and adults, we performed in vivo experiments using a mouse model of AD.A vitamin D analogue (calcipotriol; MC903) or vehicle (Ethanol) was topically applied to the ears of C57BL6 wild-type mice at 2 weeks (infant mice) or 9 weeks of age (adult mice)...T2 inflammation was more severe in infant mice than in adult mice, probably due to the former
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Trial completion date: Calcipotriol as a Novel Treatment for Central Centrifugal Cicatricial Alopecia (CCCA) (clinicaltrials.gov) - Feb 2, 2023
P1, N=10, Not yet recruiting,
Rationale:To clarify why the pathogenesis of atopic dermatitis (AD) reportedly differs between infants and adults, we performed in vivo experiments using a mouse model of AD.A vitamin D analogue (calcipotriol; MC903) or vehicle (Ethanol) was topically applied to the ears of C57BL6 wild-type mice at 2 weeks (infant mice) or 9 weeks of age (adult mice)...T2 inflammation was more severe in infant mice than in adult mice, probably due to the former Trial completion date: Sep 2023 --> Dec 2023
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: The mechanism of oxymatrine on atopic dermatitis in mice based on SOCS1/JAK-STAT3 pathway. (Pubmed Central) - Jan 28, 2023
C57BL/6 mice were induced to establish AD model by smearing carbotriol (MC903) on their back...Compared with the model group, the above pathological damage of the mice was reduced, and the serum inflammatory factors, JAK-STAT3 pathway protein, and CD3 positive expression were decreased as a dose-dependant manner (p < .05), and the expression of suppressor of cytokine signaling 1 protein was increased as a dose-dependent manner (p < .05). Oxymatrine can improve the skin inflammation symptoms of AD mice by up regulating the expression of suppressor of cytokine signaling 1, inhibiting the activation of JAK-STAT3 pathway and blocking the activation of T lymphocytes.
- |||||||||| Daliresp (roflumilast) / AstraZeneca, Takeda, AbbVie, Zoryve (roflumilast cream) / Arcutis
Journal: Topical roflumilast (Zoryve) for plaque psoriasis. (Pubmed Central) - Jan 19, 2023
Oxymatrine can improve the skin inflammation symptoms of AD mice by up regulating the expression of suppressor of cytokine signaling 1, inhibiting the activation of JAK-STAT3 pathway and blocking the activation of T lymphocytes. No abstract available
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Involucrin modulates vitamin D receptor activity in the epidermis. (Pubmed Central) - Jan 16, 2023
Coinciding with the dampened MC903-mediated inflammation, skin microbiota of Ivl -/- mice was more stable compared to WT mice, which exhibited a MC903-responsive increase in Bacteroidetes and decrease in Firmicutes. Together, our studies in Ivl -/- mice identify a functional role for Involucrin to positively impact Vdr activity and suggest an emerging IVL/VDR paradigm for adaptation in the human epidermis.
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