Lack of Endogenous Annexin A1 Increases Mast Cell Activation and Exacerbates Experimental Atopic Dermatitis

Annexin A1 (AnxA1) is a protein with potent anti-inflammatory actions and an interesting target that has been poorly explored in skin inflammation. This work evaluated the lack of endogenous AnxA1 in the progression of ovalbumin (OVA)-induced atopic dermatitis (AD)-like skin lesions. OVA/Alum-immunized C57BL/6 male wild-type (WT) and AnxA1 null (AnxA1-/-) mice were challenged with drops containing OVA on days 11, 14–18 and 21–24. The AnxA1-/- AD group exhibited skin with intense erythema, erosion and dryness associated with increased skin thickness compared to the AD WT group. The lack of endogenous AnxA1 also increased IgE relative to WT animals, demonstrating exacerbation of the allergic response. Histological analysis revealed intense eosinophilia and mast-cell activation in AD animals, especially in AnxA1-/-. Both AD groups increased skin interleukin (IL)-13 levels, while IL-17A was upregulated in AnxA1-/- lymph nodes and mast cells. High levels of phosphorylated ERK were detected in keratinocytes from AD groups. However, phospho-ERK levels were higher in the AnxA1-/- when compared to the respective control groups. Our results suggest AnxA1 as an important therapeutic target for inflammatory skin diseases.

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Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels, Orai-1 and TRPV3, and Mast Cell Activation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/8312946 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Seok Yong Kang ◽

Hyo Won Jung ◽

Joo Hyun Nam ◽

Woo Kyung Kim ◽

Jong-Seong Kang ◽

...

Keyword(s):

Atopic Dermatitis ◽

Mast Cell ◽

Calcium Channels ◽

Cell Activation ◽

Inflammatory Cells ◽

Skin Inflammation ◽

Mast Cell Activation ◽

Tribulus Terrestris ◽

Symptom Scores ◽

Safe Approach

Ethnopharmacological Relevance. In this study, we investigated the effects of Tribulus terrestris fruit (Leguminosae, Tribuli Fructus, TF) extract on oxazolone-induced atopic dermatitis in mice. Materials and Methods. TF extract was prepared with 30% ethanol as solvent. The 1% TF extract with or without 0.1% HC was applied to the back skin daily for 24 days. Results. 1% TF extract with 0.1% HC improved AD symptoms and reduced TEWL and symptom scores in AD mice. 1% TF extract with 0.1% HC inhibited skin inflammation through decrease in inflammatory cells infiltration as well as inhibition of Orai-1 expression in skin tissues. TF extract inhibited Orai-1 activity in Orai-1-STIM1 cooverexpressing HEK293T cells but increased TRPV3 activity in TRPV3-overexpressing HEK293T cells. TF extract decreased β-hexosaminidase release in RBL-2H3 cells. Conclusions. The present study demonstrates that the topical application of TF extract improves skin inflammation in AD mice, and the mechanism for this effect appears to be related to the modulation of calcium channels and mast cell activation. This outcome suggests that the combination of TF and steroids could be a more effective and safe approach for AD treatment.

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Extracellular superoxide dismutase ameliorates house dust mite-induced atopic dermatitis-like skin inflammation and inhibits mast cell activation in mice

Experimental Dermatology ◽

10.1111/exd.13028 ◽

2016 ◽

Vol 25 (8) ◽

pp. 630-635 ◽

Cited By ~ 5

Author(s):

Yun Sang Lee ◽

Jung-Hye Choi ◽

Ji-Hyun Lee ◽

Han-Woong Lee ◽

Weontae Lee ◽

...

Keyword(s):

Superoxide Dismutase ◽

Atopic Dermatitis ◽

Mast Cell ◽

House Dust ◽

House Dust Mite ◽

Cell Activation ◽

Skin Inflammation ◽

Mast Cell Activation ◽

Extracellular Superoxide Dismutase ◽

Dust Mite

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Benzo[a]pyrene aggravates atopic dermatitis-like skin lesions in mice

Human & Experimental Toxicology ◽

10.1177/09603271211036123 ◽

2021 ◽

pp. 096032712110361

Author(s):

Rie Yanagisawa ◽

Eiko Koike ◽

Hirohisa Takano

Keyword(s):

Atopic Dermatitis ◽

Mast Cell ◽

Lymph Nodes ◽

T Cell Activation ◽

Cell Activation ◽

Systemic Exposure ◽

Skin Inflammation ◽

Skin Lesions ◽

Mite Allergen ◽

Regional Lymph Nodes

Background: Benzo[a]pyrene (BaP) affects the immune system and causes mutagenic and carcinogenic effects. Purpose: We aimed to evaluate the effects of systemic exposure to BaP on mite allergen–induced atopic dermatitis (AD)–like skin lesions in mice. Methods: Mite allergen ( Dermatophagoides pteronyssinus; Dp) was injected intradermally into the right ears of NC/Nga male mice on eight occasions every 2–3 days. Benzo[a]pyrene was administered intraperitoneally in the equivalent doses of 0, 2, 20, 200, or 2000 μg/kg/day, once a week on four occasions. Results: AD-like skin inflammation related to mite allergen worsened by BaP exposure at 2, 20 µg/kg/day doses; this was in parallel with eosinophil and mast cell infiltration and mast cell degranulation. A trend was also observed toward increased proinflammatory molecule expression, including macrophage inflammatory protein-1 alpha, interleukin (IL)-4, IL-13, and IL-18, in the ear tissue. However, 200 or 2000 µg/kg/day BaP attenuated the enhancing effects. In the regional lymph nodes, 2 µg/kg/day BaP with Dp enhanced antigen-presenting cell and T cell activation compared with Dp alone. Conclusions: This suggests that BaP exposure can aggravate Dp-induced AD-like skin lesions through TH2-biased responses in the inflamed sites and the activation of regional lymph nodes. Therefore, BaP may be responsible for the recent increase in AD incidence.

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Regulation of Plasma Substance P and Skin Mast Cells by Odorants

Journal of Cutaneous Medicine and Surgery ◽

10.1007/s10227-002-0129-y ◽

2003 ◽

Vol 7 (4) ◽

pp. 287-291 ◽

Cited By ~ 11

Author(s):

Junichi Hosoi ◽

Masahiro Tanida ◽

Toru Tsuchiya

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Substance P ◽

Cell Activation ◽

Immobilization Stress ◽

Skin Diseases ◽

Skin Inflammation ◽

Mast Cell Activation ◽

Itch Sensation ◽

Methyl Benzene

Background: Mast cells stimulate inflammation and itch sensation in the skin by releasing various mediators when they are activated. Stress exacerbates some skin diseases. We have reported that inhalation of certain odorants modulates immune reactions in the skin. Objective: The possible usage of odorants in the regulation of skin inflammation and itch sensation was to be examined. Methods: Female volunteers were subjected to interview stress with or without odorant inhalation. Mice were immobilized while inhaling odorants. Toluidene blue-stained sections were analyzed for activated mast cells. Plasma substance P level was determined by enzyme-linked immunoassay. Results: Interview stress induced plasma substance P only in volunteers who did not inhale odorants containing 2% 1,3-dimethoxy-5-methyl benzene (DMMB). Immobilization stress induced mast cell activation in mice and the activation was blocked by exposure to DMMB. Conclusions: Stress causes mast cell activation via an increase in substance P. The effect of stress is suppressed by inhalation of DMMB.

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