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Colloids and Surfaces. B, Biointerfaces Feb 2022We investigated the immunomodulatory and anti-inflammatory efficacy of hederagenin coating on maghemite (γ-FeO) nanoparticles (HM) in atopic dermatitis (AD), as well as...
We investigated the immunomodulatory and anti-inflammatory efficacy of hederagenin coating on maghemite (γ-FeO) nanoparticles (HM) in atopic dermatitis (AD), as well as the physical and optical properties of maghemite nanoparticles (MP) using SEM, XRD spectroscopy, UV-vis spectra, Raman spectra, and FTIR spectroscopy. Dose-dependent treatment with HM (10, 50, 100, 200 μg/mL) inhibited the expression of Interleukin-2 (IL-2) and Tumor necrosis factor- α (TNF-α) in inflammatory induced HaCaT and Jurkat cells with inflammation caused by TNF/IFN-γ and PMA/A23187. AD model was induced by performing topical application of 2,4-dinitrochlorobenzene (DNCB) and dermatophagoides farinae extract (DFE) for a 31-day period on 8-week-old BALB/c mice. The HM treatments efficiently diminished the AD-like cutaneous lesion induced by DNCB-DFE sensitization in mice. Compared to the AD-only groups, HM treatment considerably attenuated mast cell infiltration and lowered epidermal, and dermal thickness of mice ears skin. In addition, HM treatment prominently alleviated the enlarged size and weight of lymph nodes. Furthermore, HM treatment resulted in a notable reduction in the mRNA expression of Th1 cytokines (TNF-α and IFN-γ), Th2 cytokines (IL-4 and IL-6), Th17 (IL-17), and TSLP. Our data showed that HM provides better AD attenuation compared to MP. Additionally, HM had synergistic effect and act as anti-inflammatory and immunomodulatory agent. Thus, HM shows great potential in AD medication and as a substitution of non-steroid-based medication.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Atopic; Ferric Compounds; Mice; Mice, Inbred BALB C; Nanoparticles; Oleanolic Acid; Skin
PubMed: 34896691
DOI: 10.1016/j.colsurfb.2021.112244 -
Frontiers in Nutrition 2022Atopic dermatitis (AD) is a common chronic allergic skin disease characterized clinically by severe skin lesions and pruritus. L. (PO) is a resourceful plant with...
Atopic dermatitis (AD) is a common chronic allergic skin disease characterized clinically by severe skin lesions and pruritus. L. (PO) is a resourceful plant with homologous properties in medicine and food. In this study, we used two different methods to extract PO, and compared the therapeutic effects of PO aqueous extract (POAE) and PO ultrasound-assisted ethanol extract (POEE) on 2,4-dinitrochlorobenzene (DNCB)-induced AD mice. The results showed that in POAE and POEE, the extraction rates of polysaccharides were 16.95% and 9.85%, while the extraction rates of total flavonoids were 3.15% and 3.25%, respectively. Compared with AD mice, clinical symptoms such as erythema, edema, dryness and ulceration in the back and left ear were alleviated, and pruritus behavior was reduced after POAE and POEE treatments. The thickness of the skin epidermis was thinned, the density of skin nerve fibers labeled with protein gene product 9.5 (PGP9.5) was decreased, and mast cell infiltration was reduced. There was a decrease in blood lymphocytes, eosinophils and basophils, a significant decrease in spleen index and a noticeable decrease in serum immunoglobulin E (Ig E). POEE significantly reduced the concentration of the skin pruritic factor interleukin (Il)-31. POAE and POEE reduced the concentration of skin histamine (His), down-regulated mRNA expression levels of interferon-γ (Ifnγ), tumor necrosis factor-α (Tnf-α), thymic stromal lymphopoietin (Tslp) and Il-4, with an increase of Filaggrin (Flg) and Loricrin (Lor) in skin lesions. These results suggested that POAE and POEE may inhibit atopic response and alleviate the clinical symptoms of AD by inhibiting the expression of immune cells, inflammatory mediators and cytokines. PO may be a potential effective drug for AD-like diseases.
PubMed: 36051905
DOI: 10.3389/fnut.2022.986943 -
Drug Design, Development and Therapy 2021Treatment of extensive or recalcitrant alopecia areata (AA) is a major clinical challenge. Even after thorough investigation of several medications, its treatment... (Review)
Review
Treatment of extensive or recalcitrant alopecia areata (AA) is a major clinical challenge. Even after thorough investigation of several medications, its treatment outcomes have remained unsatisfactory. While there is no US Food and Drug Administration-approved medication for AA yet, topical immunotherapy has been a well-documented treatment option. Dinitrochlorobenzene, squaric acid dibutylester, and diphenylcyclopropenone are three substances that have demonstrated efficacy in the treatment of extensive or recalcitrant AA. Despite being commonly used, the mechanism underlying topical immunotherapy is not well-elucidated and a wide range of clinical efficacies have been reported in the literature. The aim of this review was to summarize and update the pharmacology, mechanism of action, therapeutic efficacy, and tolerability of topical immunotherapy in the treatment of AA.
Topics: Adjuvants, Immunologic; Administration, Topical; Alopecia Areata; Humans; Immunologic Factors; Immunotherapy
PubMed: 33790540
DOI: 10.2147/DDDT.S297858 -
Journal of Ethnopharmacology Jun 2023Lonicera japonica Thunb. is a traditional medicinal herb with a long history owing to its widespread use in Asia for the treatment of several inflammatory diseases...
ETHNOPHARMACOLOGICAL RELEVANCE
Lonicera japonica Thunb. is a traditional medicinal herb with a long history owing to its widespread use in Asia for the treatment of several inflammatory diseases including allergic dermatitis; however, its active components and mechanism of action have not been fully elucidated.
AIM OF THE STUDY
In this study, a homogeneous polysaccharide with strong anti-inflammatory effects was extracted from the traditional Chinese medicine Lonicera japonica. The mechanism by which the polysaccharide WLJP-025p regulates p62 to activate Nrf2, promote NLRP3 inflammasome degradation, and improve AD was investigated.
MATERIALS AND METHODS
An AD model was established using DNCB, and saline was used as a control. The WLJP-L and WLJP-H groups were administered 30 and 60 mg/kg WLJP-025p during the model challenge period, respectively. The therapeutic effect of WLJP-025p was evaluated by determining the skin thickness, performing HE and toluidine blue staining, detecting TSLP via IHC, and determining serum IgE and IL-17 levels. Th17 differentiation was detected using flow cytometry. IF and WB were performed to evaluate the expression levels of c-Fos, p-p65, NLRP3 inflammatory bodies, autophagy pathway, ubiquitination, and Nrf2 proteins.
RESULTS
WLJP-025p significantly inhibited DNCB-induced skin hyperplasia and pathological abnormalities and increased TSLP levels in mice. The differentiation of Th17 in the spleen, IL-17 release, p-c-Fos, p-p65 protein expression, and NLRP3 inflammasome activation in the skin tissues were reduced. Furthermore, p62 expression, p62 Ser403 phosphorylation, and ubiquitinated proteins were increased.
CONCLUSIONS
WLJP-025p improved AD in mice by upregulating p62 to activate Nrf2 and promote the ubiquitination and degradation of NLRP3.
Topics: Mice; Animals; Dermatitis, Atopic; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; NF-E2-Related Factor 2; Interleukin-17; Lonicera; Dinitrochlorobenzene; Polysaccharides
PubMed: 36889421
DOI: 10.1016/j.jep.2023.116344 -
Inflammation Apr 2024The mouse model of 2,4-dinitrochlorbenzene (DNCB)-induced human-like atopic dermatitis (hlAD) has been widely used to test novel treatment strategies and compounds....
The mouse model of 2,4-dinitrochlorbenzene (DNCB)-induced human-like atopic dermatitis (hlAD) has been widely used to test novel treatment strategies and compounds. However, the study designs and methods are highly diverse, presenting different hlAD disease patterns that occur after sensitization and repeated challenge with DNCB on dorsal skin. In addition, there is a lack of information about the progression of the disease during the experiment and the achieved pheno- and endotypes, especially at the timepoint when therapeutic treatment is initiated. We here examine hlAD in a DNCB-induced BALB/cJRj model at different timepoints: (i) before starting treatment with dexamethasone, representing a standard drug control (day 12) and (ii) at the end of the experiment (day 22). Both timepoints display typical AD-associated characteristics: skin thickening, spongiosis, hyper- and parakeratosis, altered cytokine and gene expression, increased lipid mediator formation, barrier protein and antimicrobial peptide abnormalities, as well as lymphoid organ hypertrophy. Increased mast cell infiltration into the skin and elevated immunoglobulin E plasma concentrations indicate a type I allergy response. The DNCB-treated skin showed an extrinsic moderate sub-acute hlAD lesion at day 12 and an extrinsic mild sub-acute to chronic pheno- and endotype at day 22 with a dominating Th2 response. A dependency of the filaggrin formation and expression in correlation to the disease severity in the DNCB-treated skin was found. In conclusion, our study reveals a detailed classification of a hlAD at two timepoints with different inflammatory skin conditions and pheno- and endotypes, thereby providing a better understanding of the DNCB-induced hlAD model in BALB/cJRj mice.
Topics: Dermatitis, Atopic; Animals; Dinitrochlorobenzene; Mice; Filaggrin Proteins; Disease Models, Animal; Mice, Inbred BALB C; Skin; Cytokines; Dexamethasone; Inflammation; Female
PubMed: 38150167
DOI: 10.1007/s10753-023-01943-x -
Allergy, Asthma & Immunology Research Sep 2022The beneficial effects of a combination therapy using and galactooligosaccharide (GOS) for the treatment of atopic dermatitis (AD) have not been elucidated.
PURPOSE
The beneficial effects of a combination therapy using and galactooligosaccharide (GOS) for the treatment of atopic dermatitis (AD) have not been elucidated.
METHODS
Gene expressions of interleukin (IL)-4 and IL-13 from peripheral blood mononuclear cells and fecal abundance of . from 12-month-old infants were evaluated. Human primary epidermal keratinocytes (HEKs) and hairless mice were treated with , GOS, -derived extracellular vesicles (BLEVs), dinitrochlorobenzene (DNCB), or a synbiotic mixture of . and GOS. Expression of epidermal barrier proteins and cytokines as well as serum immunoglobulin E (IgE) levels were analyzed in HEKs and mice. Dermatitis scores, transepidermal water loss (TEWL), epidermal thickness, and fecal abundance were evaluated in mice.
RESULTS
Fecal abundance of . was negatively correlated with blood expression in infants. or BLEVs increased expression of filaggrin () and loricrin () in HEKs. . increased the efficacy of GOS to upregulate and expressions in HEKs. Oral administration of GOS increased fecal abundance of . in mice. Oral administration of . attenuated DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, and deficiency of epidermal barrier proteins. Moreover, the combination of and GOS showed greater effects to improve DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, serum IgE levels, over-expression, and the deficiency of epidermal barrier proteins than the administration of alone.
CONCLUSIONS
and GOS improve DNCB-induced skin barrier dysfunction and AD-like skin.
PubMed: 36174995
DOI: 10.4168/aair.2022.14.5.549 -
International Immunopharmacology Sep 2023Atopic dermatitis (AD) is a common chronic inflammatory skin disease causing erythema and itching. The etiology of AD is complex and not yet clear. Vitamin D is a...
Atopic dermatitis (AD) is a common chronic inflammatory skin disease causing erythema and itching. The etiology of AD is complex and not yet clear. Vitamin D is a fat-soluble vitamin that promotes skin cell growth and differentiation and regulates immune function. This study aimed to explore the therapeutic effect of calcifediol, the active metabolite of vitamin D, on experimental AD and the possible mechanism of action. We found that the levels of vitamin D binding protein (VDBP) and vitamin D receptor (VDR) in biopsy skin samples from AD patients decreased compared with controls. We used 2,4-dinitrochlorobenzene (DNCB) to induce an AD mouse model on the ear and back of BALB/c mice. A total of five groups were used: the control group, the AD group, the AD + calcifediol group, the AD + dexamethasone group, and the calcifediol alone group. Under calcifediol treatment, mice exhibited reduced spinous layer thickening, reduced inflammatory cell infiltration, downregulated aquaporin 3 (AQP3) expression, and restored the barrier function of the skin. Simultaneous calcifediol treatment decreased STAT3 phosphorylation, inhibited inflammation and chemokine release, decreased AKT1 and mTOR phosphorylation, and suppressed epidermal cell proliferation and abnormal differentiation. In conclusion, our study demonstrated that calcifediol significantly protected mice against DNCB-induced AD. In a mouse model of AD, calcifediol may reduce inflammatory cell infiltration and chemokines by inhibiting the phosphorylation of STAT3 and may restore skin barrier function through the downregulation of AQP3 protein expression and inhibition of cell proliferation.
Topics: Mice; Animals; Dermatitis, Atopic; Dinitrochlorobenzene; Vitamin D; Calcifediol; Skin; Chemokines; Vitamins; Immunity; Mice, Inbred BALB C; Cytokines
PubMed: 37393836
DOI: 10.1016/j.intimp.2023.110558 -
Molecular Immunology Nov 2022Deinococcus radiodurans is an extremophile, well known to be extremely resistant to external stresses due to its unique physiological system and structure of cellular...
Deinococcus radiodurans is an extremophile, well known to be extremely resistant to external stresses due to its unique physiological system and structure of cellular components. Although the proportion of D. radiodurans has been reported to be negatively correlated with atopic dermatitis, the exact function of D. radiodurans in allergic diseases and its precise mechanisms have not been studied. In the present study, we hypothesize that D. radiodurans or its cellular constituents play a critical role in the skin to prevent allergic inflammatory responses by modulating immunity. Heat-killed D. radiodurans inhibited the production of Th2 cytokines, such as IL-4 and IL-5, induced by ovalbumin (OVA) stimulation in splenocytes from OVA-sensitized mice. Among the cellular constituents of D. radiodurans, such as cell wall (DeinoWall), cell membrane (DeinoMem), and exopolysaccharide (DeinoPol), only DeinoWall inhibited the production of Th2 cytokines and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD), a Th2-predominant allergic disease in mice. Moreover, serum IgE levels and infiltration of mast cells into skin lesions, the markers of Th2 response induced by DNCB application, were significantly inhibited by treatment with DeinoWall. Remarkably, DeinoWall induced the maturation of bone marrow-derived dendritic cells (BMDCs) that promote Th1-biased immunity, which might balance Th1/Th2 and regulate allergic inflammatory responses. Collectively, these results suggest that DeinoWall acts as a major cellular constituent in the negative regulation of allergic inflammatory responses by D. radiodurans and might be a viable candidate for the treatment of allergic diseases.
Topics: Animals; Anti-Allergic Agents; Cell Wall; Cytokines; Deinococcus; Dermatitis, Atopic; Dinitrochlorobenzene; Immunoglobulin E; Interleukin-4; Interleukin-5; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells
PubMed: 36113363
DOI: 10.1016/j.molimm.2022.09.004 -
Experimental Dermatology Dec 2021Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder with few treatment options. Dynamin-related protein 1 (Drp1)-dependent mitochondrial fission...
Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder with few treatment options. Dynamin-related protein 1 (Drp1)-dependent mitochondrial fission contributes to the activation of NLRP3 inflammasome, and inhibiting Drp1 has been become an attractive therapeutic strategy for inflammatory diseases. This study aimed to investigate the effects of Drp1 inhibitor mdivi-1 on experimental AD. We firstly detected the effects of mdivi-1 on primary human keratinocytes in an inflammatory cocktail-induced AD-related inflammation in vitro. Results showed that mdivi-1 inhibited NLRP3 inflammasome activation and pyroptosis which were evidenced by decreased expression of NLRP3, ASC, cleavage of caspase-1, GSDMD-NT, mature interleukin (IL)-1β and IL-18 in keratinocytes under AD-like inflammation. Next, mouse model of AD-like skin lesions was induced by epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) and mdivi-1 (25 mg/kg/day, days 5-33 during construction of AD model) was intraperitoneally injected into DNCB-induced mice. AD mice with mdivi-1 treatment exhibited ameliorated AD symptoms, lower serum IgE level, and reduced epidermal thickening, mast cells infiltration, and production of IL-4, IL-5 and IL-13 in the lesional tissues. Indeed, mdivi-1 significantly inhibited NLRP3 inflammasome activation and pyroptotic injury occurred in DNCB-treated skin tissues. Mechanically, mdivi-1 regulated the expression of mitochondrial dynamic proteins and suppressed the activation of NF-κB signal pathway which is an upstream of NLRP3 inflammasome both in vitro and in vivo. This study demonstrated that mdivi-1 could protect against experimental AD through inhibiting the activation of NLRP3 inflammasome and subsequent inflammatory cytokine release, and mdivi-1 might exert this function by inhibiting mitochondrial fission and subsequently blocking NF-κB pathway.
Topics: Administration, Topical; Animals; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Dynamins; Female; Humans; Inflammasomes; Keratinocytes; Mice; Mice, Inbred BALB C; NLR Family, Pyrin Domain-Containing 3 Protein; Quinazolinones
PubMed: 34133800
DOI: 10.1111/exd.14412 -
Nutrients Apr 2023Atopic dermatitis is a chronic skin disease that affects millions of people all over the world. The objective of this study was to evaluate the inhibitory effects of the...
Atopic dermatitis is a chronic skin disease that affects millions of people all over the world. The objective of this study was to evaluate the inhibitory effects of the roots of (GU) and Donkey Hide Gelatin (DHG) water extracts on DNCB-induced NC/Nga mice and TNF-α/IFN-γ treated keratinocytes or LPS-stimulated macrophages. The combined treatment using the water extracts of GU and DHG improved the skin symptom evaluation score and skin histology, with increased expression of the skin barrier proteins Claudin 1 and Sirt 1 in lesion areas. The IFN-γ activity was promoted in PBMCs, ALN, and dorsal skin tissue, while the absolute cell number was reduced for T cells so that the production and expression of serum IgE and cytokines were suppressed. In TNF-α/IFN-γ induced HaCaT cells, IL-6, IL-8, MDC, and RANTES were all inhibited by GU and DHG water extracts, while ICAM-1 and COX-2 levels were similarly downregulated. In addition, GU and DHG water extracts decreased LPS-mediated nitric oxide, IL-6, TNF-α, and PGE in RAW 264.7 cells, and the expression of iNOS and COX-2 also decreased. Notably, the DHG:GU ratio of 4:1 was shown to have the best effects of all ratios. In conclusion, GU and DHG have anti-skin inflammatory potentials that can be used as alternative ingredients in the formula of functional foods for people with atopic dermatitis.
Topics: Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Gelatin; Glycyrrhiza uralensis; Cyclooxygenase 2; Interleukin-6; Lipopolysaccharides; Tumor Necrosis Factor-alpha; Functional Food
PubMed: 37432237
DOI: 10.3390/nu15092094