Topically applied semaphorin 3A ointment inhibits scratching behavior and improves skin inflammation in NC/Nga mice with atopic dermatitis

Negi, Osamu; Tominaga, Mitsutoshi; Tengara, Suhandy; Kamo, Atsuko; Taneda, Kenichi; Suga, Yasushi; Ogawa, Hideoki; Takamori, Kenji

doi:10.1016/j.jdermsci.2012.01.007

Cited by 60 publications

(58 citation statements)

References 30 publications

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“…54,55) the therapeutic efficacy of exogenous Sema3A on atopic dermatitis-like symptoms was greater than that of current agents, such as betamethasone and tacrolimus. 55) Moreover, histological analyses showed decreases in (i) the numbers of epidermal nerve fibers; (ii) the numbers of inflammatory infiltrates; (iii) the production of cytokines; (iv) the density of dermal blood vessels; and (v) epidermal thickness in Sema3A-treated lesional skin. 54,55) these findings suggest that exogenous Sema3A not only affects sensory nerve fibers, but other cells that express neuropilin-1, include immune system cells, endothelial cells and keratinocytes.…”

Section: Sema3amentioning

confidence: 94%

“…55) Moreover, histological analyses showed decreases in (i) the numbers of epidermal nerve fibers; (ii) the numbers of inflammatory infiltrates; (iii) the production of cytokines; (iv) the density of dermal blood vessels; and (v) epidermal thickness in Sema3A-treated lesional skin. 54,55) these findings suggest that exogenous Sema3A not only affects sensory nerve fibers, but other cells that express neuropilin-1, include immune system cells, endothelial cells and keratinocytes. 56) Thus, Sema3A and its receptors are promising therapeutic targets for atopic dermatitis.…”

Section: Sema3amentioning

confidence: 98%

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An Update on Peripheral Mechanisms and Treatments of Itch

Tominaga

Takamori

2013

Biological & Pharmaceutical Bulletin

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Histamine H 1 -receptor blockers are used to treat all types of itch resulting from serious skin diseases such as atopic dermatitis, as well as from renal and liver diseases. However, they often lack efficacy in chronic itch, a profound clinical problem that decreases quality of life. The development of effective treatments requires a full understanding of the fundamental mechanisms of itch. Recent studies have indicated that the pathogenic mechanisms of itch also involve agonists other than histamine, including proteases, neuropeptides, cytokines, and opioids, as well as their cognate receptors. Release of these pruritogenic mediators and modulators into the periphery may directly activate itch-mediating C-fibers via specific receptors on the nerve terminals. Histological observations have shown increased epidermal nerve densities in patients with atopic dermatitis, suggesting that the higher density is at least partly responsible for itch sensitization. This

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Section: Sema3amentioning

confidence: 94%

Section: Sema3amentioning

confidence: 98%

An Update on Peripheral Mechanisms and Treatments of Itch

Tominaga

Takamori

2013

Biological & Pharmaceutical Bulletin

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“…A significant improvement of TEWL was recorded only in sema3A ointment-treated mice. The number of inflammatory cells, such as CD4 effector T cells and eosinophils were reduced in the epidermis of sema3A treated mice compared with controls (23). In another study, sema3A treatment has been shown to inhibit nerve growth factor-induced sprouting of sensory nerves, and the normalization of hyper innervation in AD.…”

Section: Semaphorin3a In Atopic Dermatitis (Ad)mentioning

confidence: 90%

Semaphorin3A: A potential therapeutic tool in immune-mediated diseases

Vadasz

Toubi

2018

Eur J Rheumatol

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The significance of semaphorin3A (sema3A) in regulating immune-mediated inflammation is widely reported. There are multiple mechanisms involved in the process of sema3A-mediated regulation. One of them is the ability of sema3A to maintain a sufficient regulation of both T-cell and B-cell activation. Because it is involved in the pathogenesis of many autoimmune, infectious, and malignant diseases, sema3A turns to be a promising therapeutic tool to be studied and applied in these diseases. Keywords: Semaphorin 3A, immune mediated diseases, atopic diseases the other, it increased the serum level of the anti-inflammatory cytokine IL-10 (11). In line with these findings, sema3A expression was found to be decreased on CD4 + T cells of RA patients, whereas NP-1 expression on these cells was increased. CD4+NP-1+T cells, known as T regulatory cells and a source of IL-10, were reported to be decreased in RA. In this case, the addition of sema3A into a co-culture with T cells acts directly on CD4+NP-1+T cells and increases IL-10 production, supporting its therapeutic beneficial effect in RA (11). In a recent study, the expression of sema3A in synovial tissues of RA patients was investigated. Disease activity and the histological features of synovial tissues were also assessed in relation to sema3A expression. Human synovial tissues were obtained from established RA patients, compared those of patients suffering from osteoarthritis (OA), and assessed for sema3A, VEGF-A, and NP-1mRNA expression, using quantitative real-time polymerase chain reaction (qPCR). The protein expression of sema3A in synovial lining cells was decreased in RA tissues compared with that in OA samples. Sema3A mRNA levels correlated with the inflammation score, namely with the extent of lymphocyte infiltration (R=0.50, p=0.004). Thus, the correlation of sema3A expression in RA synovial tissues may become a therapeutic target in RA (12).Semaphorin3A and systemic lupus erythematosus (SLE): Hypothesizing that sema3A may have a similar role in SLE, we assessed its serum levels in SLE patients. Sema3A serum levels in SLE patients were found to be significantly lower than in RA patients (55.04±16.30 ng/mL vs. 65.54±14.82 ng/mL, p=0.018) and lower yet than in normal individuals (55.04±16.30 ng/ mL vs. 74.41±17.60 ng/mL, p<0.0001). Serum sema3A levels in SLE patients were low in negative correlation with SLE disease activity, renal damage, and the presence of relevant autoantibodies (R= −0.89, p<0.0001) (13). Being the source of autoantibodies and pro-inflammatory cytokines, the regulatory status of B cells was evaluated. The expression of sema3A on B regulatory (Breg) cells, namely CD19 + CD25high and NP-1 + was analyzed. As expected sema3A expression on these cells was significantly lower in SLE patients when compared to B cells from normal individuals, suggesting this to be in part responsible for B-cell auto-reactivity in SLE. Our other finding was the down-regulation of NP-1 expression on B cells from SLE patients, suggesting that both sema3A and N...

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“…A significant improvement of transepidermal water loss was observed only in sema3A-ointment-treated mice, as was a reduction in the densities of nerve fibers in the epidermis and the numbers of inflammatory cells, such as CD4 immunoreactive T cells and eosinophils. Here again, it was suggested that sema3A ointment may have therapeutic efficacy in patients with pruritus and AD [43] (fig. 1b).…”

Section: Atopic Dermatitis and The Role Of Sema3amentioning

confidence: 99%

The Role of B Regulatory Cells and Semaphorin3A in Atopic Diseases

Vadasz

Haj²,

Toubi³

2014

Int Arch Allergy Immunol

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When the pathogenesis of allergic inflammatory diseases such as asthma, allergic rhinitis and atopic dermatitis is discussed, one should take into consideration the involvement of regulatory cells/molecules whose role is to prevent the induction and/or deterioration of such diseases. The involvement of T regulatory cells and FoxPp3 is well established in asthma, but only little is known about the involvement of B regulatory cells (Bregs) and the soluble regulatory molecule semaphorin3A (sema3A) in atopic diseases. During the last decade, research has sought to better define the various subtypes of Breg cells and how similar they are to their parallel subtypes of Tregs. In this review, we focus on the newly reported role of Bregs in both experimental and human models of asthma. Bregs are also involved in the pathophysiology of food allergy. We also show how sema3A plays a role in the pathogenesis of allergic rhinitis and atopic dermatitis. Determining the above processes could facilitate the use of regulatory molecules as therapeutic tools in treating these diseases.

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Topically applied semaphorin 3A ointment inhibits scratching behavior and improves skin inflammation in NC/Nga mice with atopic dermatitis

Cited by 60 publications

References 30 publications

An Update on Peripheral Mechanisms and Treatments of Itch

An Update on Peripheral Mechanisms and Treatments of Itch

Semaphorin3A: A potential therapeutic tool in immune-mediated diseases

The Role of B Regulatory Cells and Semaphorin3A in Atopic Diseases

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