In vivo transfection of a cis element ‘decoy’ against signal transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity

Sumi, Koji; Yokozeki, Hiroo; Wu, Minghua; Satoh, Takahiro; Kaneda, Yasufumi; Takeda, Kiyoshi; Akira, Shizuo; Nishioka, Kiyoshi

doi:10.1038/sj.gt.3302345

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…34 Topical administration of an NF-kB dODN has been successfully tested in a mouse model of atopic dermatitis 35 (in comparison with betametasone 36 ), as well as in the DTH response of the same species, 37 but the potentially adverse proapoptotic effects of blocking this transcription factor must be followed. Recently, dODN blockade of STAT3, which together with NF-kB and STAT1 is implicated in psoriasis, 7 has revealed its therapeutic potential in a genetically engineered mouse model of the disease.…”

Section: Discussionmentioning

confidence: 99%

Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity

Wagner

Wittjen

Stojanović

et al. 2008

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 99%

Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity

Wagner

Wittjen

Stojanović

et al. 2008

Journal of Allergy and Clinical Immunology

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“…Recent studies have demonstrated therapeutic applications of several decoy ODNs targeting transcription factors including NF-kB, [35][36][37] AP-1, 38-40 E2F, 54 Sp1, 55,56 and the signal transducer and activator of transcription (STAT) family. 57,58 There have also been a few reports suggesting an active role of AP-1 during the pathogenesis of IBD. Ishiguro et al 31 These observations suggest that control of AP-1 signaling may be a potent therapeutic target for treating IBD.…”

Section: Effects Of Decoy Odns On Expression Of Proinflammatory Cytokmentioning

confidence: 99%

Decoy oligodeoxynucleotide targeting activator protein-1 (AP-1) attenuates intestinal inflammation in murine experimental colitis

Moriyama

Ishihara

Rumi

et al. 2008

Laboratory Investigation

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Various therapies are used for inflammatory bowel diseases (IBD), though none seem to be extremely effective. AP-1 is a major transcription factor that upregulates genes involved in immune and proinflammatory responses. We investigated decoy oligodeoxynucleotide (ODN) targeting AP-1 to prevent dextran sulfate sodium (DSS)-induced colitis in mice. Functional efficacies of synthetic decoy and scrambled ODNs were evaluated in vitro by a reporter gene luciferase assay and measuring flagellin-induced IL-8 expression by HCT-15 cells transfected with ODNs. Experimental colitis was induced in mice with a 2.5% DSS solution in drinking water for 7 days, and decoy or scrambled ODNs were intraperitoneally injected from days 2 to 5. Colitis was assessed by weight loss, colon length, histopathology, and detection of myeloperoxidase (MPO), IL-1b, and TNF-a in colon tissue. Therapeutic effects of AP-1 and NF-kB decoy ODNs were compared. Transfection of AP-1 decoy ODN inhibited AP-1 transcriptional activity in reporter assays and flagellin-induced IL-8 production in vitro. In mice, AP-1 decoy ODN, but not scrambled ODN, significantly inhibited weight loss, colon shortening, and histological inflammation induced by DSS. Further, AP-1 decoy ODN decreased MPO, IL-1b, and TNF-a in colonic tissue of mice with DSS-induced colitis. The AP-1 decoy therapeutic effect was comparable to that of NF-kB decoy ODN, which also significantly decreased intestinal inflammation. Double-strand decoy ODN targeting AP-1 effectively attenuated intestinal inflammation associated with experimental colitis in mice, indicating the potential of targeting proinflammatory transcription factors in new therapies for IBD.

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“…20,21 To determine whether STAT6 plays a critical role in P-selectin expression, we prepared STAT6 decoy ODNs and treated HDMECs with the ODNs after incubation with substance P. In vitro treatment of HDMECs with STAT6 decoy ODNs reduced substance P-induced P-selectin expression (Figure 8). Similarly, IL-4-induced P-selectin expression was inhibited by STAT6 decoy ODNs.…”

Section: Transfection Of a Cis Element Decoy Against Stat6-binding Simentioning

confidence: 99%

STAT-6-Mediated Control of P-Selectin by Substance P and Interleukin-4 in Human Dermal Endothelial Cells

Miyazaki

Satoh

Nishioka

et al. 2006

The American Journal of Pathology

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P-Selectin expressed on endothelial cells contributes to acute and chronic inflammation by promoting leukocyte tethering/rolling. Despite increasing evidence of P-selectin expression on human umbilical vein endothelial cells in vitro , the regulatory mechanisms of P-selectin expression on dermal endothelial cells in skin diseases are not fully understood. Here , we demonstrate increased expression of P-selectin in dermal vessels of regional skin in urticaria and atopic dermatitis. The present in vitro analyses with human dermal microvascular endothelial cells (HDMECs) revealed that histamine rapidly induced P-selectin expression. Interleukin (IL)-4 and IL-13 induced prolonged expression of surface P-selectin by HDMECs. A combination of tumor necrosis factor-␣ and IL-4 inhibited P-selectin expression. Pretreatment of HDMECs with tumor necrosis factor-␣ followed by incubation with IL-4 markedly increased P-selectin expression. Notably , incubation with substance P alone induced prolonged P-selectin expression. Activation of STAT6 appears to be a key factor in P-selectin expression induced by substance P and IL-4 because treatment with STAT6 decoy oligodeoxynucleotides significantly inhibited P-selectin expression. The present results indicate that novel , complex mechanisms are involved in endothelial P-selectin expression in the skin. STAT6 in dermal endothelial cells appears to be a potent target for controlling cellular infiltrate in allergic and/or neuroinflammatory skin diseases. Selectins expressed by endothelial cells interact with leukocyte counterreceptors and mediate the initial adhesion of leukocytes and their rolling along endothelial surfaces. Several lines of evidences indicate that endothelial selectins play important roles in inflammation. Mice lacking E-, P-, and/or L-selectins exhibit reduced leukocyte rolling and reduced extravasation of neutrophils in thioglycolate-induced peritonitis.1 P-and E-selectins are also essential for the development of irritation dermatitis and allergic contact hypersensitivity.2 Previous studies indicate that eosinophils have marked avidity for P-selectin, but not E-selectin.3-5 In mice, P-selectin deficiency causes reduced eosinophil rolling and reduced tissue eosinophilia in rag-weed peritonitis.

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In vivo transfection of a cis element ‘decoy’ against signal transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity

Cited by 18 publications

References 33 publications

Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity

Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity

Decoy oligodeoxynucleotide targeting activator protein-1 (AP-1) attenuates intestinal inflammation in murine experimental colitis

STAT-6-Mediated Control of P-Selectin by Substance P and Interleukin-4 in Human Dermal Endothelial Cells

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