A Derivative of<scp>L</scp>-Allo Threonine Alleviates 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis Indications

Heo, Jin‐Chul; Son, Hyeong-U; Kim, Solomon L.; Lee, Sang‐Han

doi:10.1271/bbb.120258

Cited by 5 publications

(6 citation statements)

References 23 publications

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“…Previously, we produced a unique chemical library using a combinatorial chemistry technique. LX519290 was a hit derived from this library and exhibited anti-atopic dermatitis [ 6 ] and anti-asthmatic activity [ 7 ]. Therefore, this protective effect may confer an avenue for preventive and curative approaches by anti-oxidation and anti-inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…LX519290 has been previously screened by Heo et al for anti-atopic and anti-asthmatic activity [ 6 , 7 ]. The amino acid, l - allo threonine, another diastereoisomer of l -threonine, is not naturally existing in the human whole body and is a component of globomycin which is a peptide antibiotic exhibiting spheroplast-forming activity [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Novel Compound LX519290, a Derivative of l-allo Threonine, on Antioxidant Potential in Vitro and in Vivo

Chun

Alam

Son

et al. 2016

IJMS

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We investigated the antioxidative activity of LX519290, a derivative of l-allo threonine, in vitro and in vivo. To evaluate the antioxidative activity of LX519290, we performed several in vitro assays (2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical-scavenging assays, a ferric reducing antioxidant power assay, cupric-reducing antioxidant capacity, and oxygen radical absorbance capacity assay) and evaluated inhibition against the generation of nitric oxide (NO) and reactive oxygen species (ROS) in murine macrophage (RAW264.7) cells. The results showed that LX519290 possessed very strong radical scavenging activity and reducing power, and inhibited NO and ROS generation in a dose-dependent manner without showing any cytotoxicity. LX519290 treatment also increased the total thiol content and glutathione S-transferases (GST) activities in RAW264.7 cells. Finally, we also determined whether LX519290 affects the mRNA levels of antioxidant enzymes in vitro and in vivo. The expression of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were markedly higher in the sample-treated group than in the oxidative stress group. LX519290 treatment also increased the transcriptional and translational activities of NF-E2-related factor-2 (Nrf-2) with corresponding increases in the transcriptional and translational activities of haeme oxygenase-1 (HO-1). Collectively, the data demonstrated that LX519290 has potent antioxidative activity, decreases NO and ROS generation, increases total thiol content and GST activities in RAW264.7 cells, and increases the transcriptional and translational levels of antioxidant enzymes in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Novel Compound LX519290, a Derivative of l-allo Threonine, on Antioxidant Potential in Vitro and in Vivo

Chun

Alam

Son

et al. 2016

IJMS

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“…Second-generation sequencing and a combined literature analysis was performed in the current study. The results revealed that the potential molecular target of miR-146a was SUMO1 (21). To functionally determine whether miR-146a has a direct effect on SUMO1 activation, vectors encoding a partial sequence of the 3′UTR of SUMO1 mRNA were utilized, where the predicted miR-146a target sites were located (Fig.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‑146a as a potential regulator involved in the pathogenesis of atopic dermatitis

Yan

Meng

et al. 2019

Mol Med Report

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Previous studies have demonstrated that microrna (mir)-146a is involved in the inflammatory response of atopic dermatitis (ad). The aim of the present study was to investigate the expression of mir-146a in the serum of patients with ad and in skin lesions of ad animal models. in addition, we aimed to predict and verify the target genes of mir-146a. mir-146a expression was measured in ad patient serum via reverse transcription-quantitative Pcr. T-helper (Th)1 [cd4 + ; interferon (iFn)-γ + ] and Th2 [cd4 + ; interleukin (il)-4 + ] expression in peripheral blood mononuclear cells was evaluated using flow cytometry. Following the establishment of a 2,4-dinitrofluorobenzene-induced c57Bl/6 mouse ad model, Th1 (cd4 + iFn-γ +) and Th2 (cd4 + il-4 +) expression was analyzed in murine spleen cells via flow cytometry. Plasmids were transfected into 293T cells and at 48 h post-transfection, cells were analyzed using a luciferase assay system. The results revealed that the AD group had a significantly lower Th1/Th2 ratio and a significantly higher miR-146a expression compared with the control group (P<0.05). Furthermore, a decreased Th1/Th2 ratio and a significantly increased miR-146a expression were observed in the model group compared with the control group (P<0.01). We also conducted a dual-luciferase assay to determine whether small ubiquitin-related modifier 1 (SUMO1) if the target gene of mir-146a. We observed a ~30% decrease in the relative luciferase activity in cells containing the 3'-untranslated region of SuMo1 + mir-146a). The results of the luciferase assay indicated that may be a direct mrna target of mir-146a; however, the quantification of band density of SUMO1 expression following western blotting did not significantly differ. The development of animal models in ad research is of vital importance. The results revealed that mir-146a may be a potential regulator involved in the pathogenesis of ad. Furthermore, the current study determined that mir-146a could be a valuable marker of ad and thus, may be applied in the development of therapeutic strategies for treating ad.

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“…1. The detailed protocol used for preparing the compound is described elsewhere (14). Other reagents used were commercially available.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we published a study in which LX519290 exhibited anti-atopic activity in a 2,4-dinitrofluorobenzene (DNFB)-induced animal model (14). In our murine asthmatic model, a number of disease symptoms including infiltration of inflammatory cells (particularly eosinophils), loss of airway structural integrity and airway obstruction were markedly attenuate in ovalbumin (OVA)-challenged mice compared to control animals.…”

Section: Introductionmentioning

confidence: 95%

Alleviation of asthma-related symptoms by a derivative of L-allo threonine

Heo

Lee

2013

International Journal of Molecular Medicine

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Chronic asthma is characterized by inflammatory cell infiltration and tissue remodeling, leading to subepithelial inflammation. In order to evaluate the anti-asthmatic activity of LX519290, a derivative of L-allo threonine, we performed several in vitro and in vivo anti-asthmatic assays. Using ovalbumin (OVA)-sensitized C57BL/6 mice, the effects of LX519290 on lung inflammation and cytokine expression in the asthmatic animals were analyzed. Treatment with this compound increased IFN-γ and decreased IL-10 mRNA expression. LX519290 potently decreased, not only immune cell infiltration in the lung, but also IL-4 and IL-13 cytokine levels in the serum of OVA-treated mice. The results demonstrated that LX519290 decreased the pathogenesis of chronic airway injury. Evidence from our model of OVA-induced asthma demonstrated that LX519290 inhibits immune cell infiltration, mucus hypersecretion, and inflammatory cytokine production. Collectively, our findings suggest that LX519290 has the potential to ameliorate asthmatic symptoms by treating inflammatory factors in the lung.

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A Derivative ofL-Allo Threonine Alleviates 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis Indications

Cited by 5 publications

References 23 publications

Effect of Novel Compound LX519290, a Derivative of l-allo Threonine, on Antioxidant Potential in Vitro and in Vivo

Effect of Novel Compound LX519290, a Derivative of l-allo Threonine, on Antioxidant Potential in Vitro and in Vivo

MicroRNA‑146a as a potential regulator involved in the pathogenesis of atopic dermatitis

Alleviation of asthma-related symptoms by a derivative of L-allo threonine

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