EC-SOD Suppresses Contact Hypersensitivity in Mouse Skin by Impairing Langerhans Cell Migration

Na, Kwang-Min; Kim, Kyoung-Eun; Park, Sang-Tae; Kim, Taeyoon

doi:10.1038/sj.jid.5700802

Cited by 19 publications

(12 citation statements)

References 28 publications

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“…This may be explained through the fact that MoDCs, different from the mouse XS106 DCs line, do not typically secrete IL-12p70. The mere fact that ROS, in the process of antigen presentation, play a role in the activation of DCs and their interactions with T cells 35 , together with the fact that extracellular superoxide dismutase impairs LC migration and therefore suppresses mouse CHS 36 , confirms the involvement of ROS in CHS. Our study has further demonstrated the involvement of ROS in CHS through hapten-induced ROS production in human MoDCs, similar to that of the involvement of ROS in mouse CHS, which was shown through hapten-induced ROS production in mouse XS 106 DC line 9 and mouse bone marrow DCs 18 .…”

Section: Discussionmentioning

confidence: 85%

The Roles of Reactive Oxygen Species Produced by Contact Allergens and Irritants in Monocyte-derived Dendritic Cells

Byamba

Kim

et al. 2010

Ann Dermatol

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Background: Although reactive oxygen species (ROS) have been produced in both mouse bone marrow-derived dendritic cells (DCs) and XS-106 DCs by contact sensitizers and irritants in previous studies, the generation of ROS in human monocyte-derived DCs (MoDCs) and their role in contact hypersensitivity (CHS) has yet to be elucidated. Objective: The purpose of this study was to determine whether contact allergens and irritants induce ROS in MoDCs and, if so, to evaluate the role of contact allergen and irritant induced-ROS in MoDCs in CHS. Methods: Production of ROS was measured by 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) assay. Surface CD86 and HLA-DR molecules were detected by flow cytometry. Protein carbonylation was detected by Western blotting. Results: ROS were produced by contact allergens such as dinitrochlorobenzene (DNCB) and thimerosal and the irritant benzalkonium chloride (BKC). DNCB-induced, but not BKC-induced, ROS increased surface CD86 and HLA-DR molecules on MoDCs and induced protein carbonylation. These changes were reduced in the presence of antioxidant N-acetyl cysteine. Conclusion: Our results suggest that DNCB-induced ROS may be different from those induced by irritant BKC. The DNCB-induced ROS may be associated with the CHS response, because they activate surface molecules on DCs that are important for generating immune reactions.

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Section: Discussionmentioning

confidence: 85%

The Roles of Reactive Oxygen Species Produced by Contact Allergens and Irritants in Monocyte-derived Dendritic Cells

Byamba

Kim

et al. 2010

Ann Dermatol

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“…Over-expression of extracellular SOD inhibits this degradation and prevents experimental lung inflammation [32] and CHS in mice [33]. Therefore, we analyzed the ability of the strong contact sensitizer TNCB to induce ROS production in the murine keratinocyte cell line Pam212 and in the fibroblast cell line L929 in vitro (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

Contact Sensitizers Induce Skin Inflammation via ROS Production and Hyaluronic Acid Degradation

et al. 2012

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Background Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS) model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed the role of contact sensitizer induced ROS production and concomitant changes in hyaluronic acid metabolism on CHS responses. Methodology/Principal Findings We analyzed in vitro and in vivo ROS production using fluorescent ROS detection reagents. HA fragmentation was determined by gel electrophoresis. The influence of blocking ROS production and HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was analyzed in the murine CHS model. Here, we demonstrate that organic contact sensitizers induce production of reactive oxygen species (ROS) and a concomitant breakdown of the extracellular matrix (ECM) component hyaluronic acid (HA) to pro-inflammatory low molecular weight fragments in the skin. Importantly, inhibition of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well as elicitation of CHS. Conclusions/Significance These data identify an indirect mechanism of contact sensitizer induced innate inflammatory signaling involving the breakdown of the ECM and generation of endogenous danger signals. Our findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors in prevention and treatment of ACD.

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“…Recently, our groups have shown that SOD3 can inhibit Ultraviolet B-induced skin inflammation, hyaluronic acid fragment-mediated skin inflammation, contact hypersensitivity, and allergic airway inflammation in mice models (21)(22)(23)33). Ross et al also demonstrated that SOD3 plays a key role in regulating inflammation in collagen-induced arthritis (43).…”

Section: Innovationmentioning

confidence: 97%

Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice

Sah

Kim

Yun

et al. 2016

Antioxidants & Redox Signaling

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Aims: The immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs) have been proposed in several autoimmune diseases and successfully tested in animal models, but their contribution to psoriasis and underlying pathways remains elusive. Likewise, an increased or prolonged presence of reactive oxygen species and aberrant antioxidant systems in skin are known to contribute to the development of psoriasis and therefore effective antioxidant therapy is highly required. We explored the feasibility of using extracellular superoxide dismutase (SOD3)-transduced allogeneic MSCs as a novel therapeutic approach in a mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation and investigated the poorly understood underlying mechanism. In addition, the chronicity and late-phase response of inflammation were evaluated during continued activation of antigen receptors by applying a booster dose of IMQ. Results: Subcutaneous injection of allogeneic SOD3-transduced MSCs significantly prevented psoriasis development in our IMQ-induced mouse model, likely through a suppression of proliferation and infiltration of various effector cells into skin with a concomitant modulated cytokine and chemokine expression and inhibition of signaling pathways such as tolllike receptor-7, nuclear factor-kappa B, p38 mitogen-activated kinase, and Janus kinase-signal transducer and activator of transcription, as well as adenosine receptor activation. Innovation and Conclusion: Our data offer a novel therapeutic approach to chronic inflammatory skin diseases such as psoriasis by leveraging immunomodulatory effects of MSCs as well as SOD3 expression. Antioxid. Redox Signal. 24, 233-248.

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EC-SOD Suppresses Contact Hypersensitivity in Mouse Skin by Impairing Langerhans Cell Migration

Cited by 19 publications

References 28 publications

The Roles of Reactive Oxygen Species Produced by Contact Allergens and Irritants in Monocyte-derived Dendritic Cells

The Roles of Reactive Oxygen Species Produced by Contact Allergens and Irritants in Monocyte-derived Dendritic Cells

Contact Sensitizers Induce Skin Inflammation via ROS Production and Hyaluronic Acid Degradation

Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice

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