The Experts below are selected from a list of 78 Experts worldwide ranked by ideXlab platform

Yan Weng - One of the best experts on this subject based on the ideXlab platform.

  • a Steroid Alkaloid derivative 02f04 upregulates thymic stromal lymphopoietin expression slowly and continuously through a novel gq 11 rock erk1 2 signaling pathway in mouse keratinocytes
    Cellular Signalling, 2019
    Co-Authors: Yan Weng, Ryosuke Segawa, Takahiro Moriya, Jingwen Wang, Zhifu Yang, Jialin Duan, Chao Guo, Ying Yin, Takayuki Yonezawa
    Abstract:

    Abstract Thymic stromal lymphopoietin (TSLP), a master switch of allergic inflammation, plays an important role in the pathogenesis of allergic diseases. Although many compounds upregulate TSLP expression in vivo or in vitro, most of them are pollutants or toxicants. In the previous study, for the first time, we found that a Steroid Alkaloid derivative 02F04, which has a unique skeletal structure compared with other TSLP-inducing chemicals, significantly induced TSLP production in mouse keratinocytes. However, it is not investigated thoroughly that how 02F04 produces TSLP and why. In this study, we did a detailed investigation on the inducible effect and underlying molecular mechanism of 02F04 on TSLP production. We found that the peak time of TSLP mRNA level induced by 02F04 at 48 h led to a slow and continuous TSLP production in PAM212 cells. Besides, 02F04-induced TSLP production was significantly suppressed by inhibitors of Rho-associated protein kinase (ROCK), guanine nucleotide-binding protein subunit alpha q/11 (Gq/11) and extracellular signal-regulated kinase 1/2 (ERK1/2) at not only protein but also mRNA levels, and by siRNA-mediated knockdown of Gq or G11. This suggested that ROCK, Gq/11 and ERK1/2 signaling pathways were involved in 02F04-induced TSLP production. Increase in the level of p-ERK1/2 induced by 02F04 was suppressed by both inhibitors of ROCK and Gq/11, indicating that ROCK and Gq/11 molecules were located at the upstream of ERK1/2 to regulate 02F04-induced TSLP production. Gq/11 was located at the upstream of ROCK because the specific Gq/11 inhibitor of YM-254890 significantly reduced 02F04-induced actin stress fiber formation. Taken together, 02F04 upregulates a slow and continuous TSLP production through a novel Gq/11-ROCK-ERK1/2 signaling pathway. The thorough understanding the effect and mechanism of 02F04 on TSLP production is expected to supply it as a novel TSLP-regulating compound and a potential new tool for investigating the role of TSLP in allergic disorders.

  • induction of thymic stromal lymphopoietin by a Steroid Alkaloid derivative in mouse keratinocytes
    International Immunopharmacology, 2018
    Co-Authors: Yan Weng, Natsumi Mizuno, Jiangxu Dong, Ryosuke Segawa, Takayuki Yonezawa, Byungyoon Cha, Jetae Woo, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
    Abstract:

    Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and exacerbating allergic diseases. Chemical compounds that induce TSLP production can enhance sensitization to antigens and exacerbate allergic inflammation. Hence, identifying such chemicals will be important to prevent an increase in allergic diseases. In the present study, we found, for the first time, that a Steroid Alkaloid derivative, code no. 02F04, concentration and time dependently induced mRNA expression and production of TSLP in a mouse keratinocyte cell line, PAM212. In particular, the activity of 02F04 was selective to TSLP. As an analogue of the liver X receptor (LXR) endogenous ligand, 02F04 rapidly increased ATP-binding cassette transporter A1 (ABCA1) expression by regulating the nuclear receptor of LXR. However, instead of being inhibited by the LXR antagonist, 02F04-induced TSLP production was delayed and markedly suppressed by inhibitors of phospholipase C (PLC), pan-protein kinase C (PKC), PKCδ, Rho-associated protein kinase (ROCK), extracellular signal-regulated kinase (ERK) 1/2, and IκΒ kinase 2 (IKK2). Treatment with 02F04 caused the formation of F-actin filaments surrounding the nucleus of PAM212 cells, which then disappeared following addition of ROCK inhibitor. 02F04 also induced phosphorylation of ERK1/2 from 2h after treatment, with a maximum at 24h, and increased nuclear factor-κB (NF-κB) promoter activity by 1.3-fold. Taken together, these results indicate that 02F04-induced TSLP production is regulated via distinct signal transduction pathways, including PLC, PKC, ROCK, ERK1/2, and NF-κB but not nuclear receptors. 02F04, with a unique skeletal structure in inducing TSLP production, can represent a potential new tool for investigating the role of TSLP in allergic diseases.

Helmut Ripperger - One of the best experts on this subject based on the ideXlab platform.

  • Steroid Alkaloid glycosides from solanum coccineum
    Phytochemistry, 1996
    Co-Authors: Susan Lorey, Andrea Porzel, Helmut Ripperger
    Abstract:

    Abstract In addition to solamargine, isoanguivine and solasonine, two new Steroid Alkaloid glycosides, xylosyl-solamargine and xylosyl-β-solamarine, have been isolated from the aerial parts of Solanum coccineum, the structures of which have been elucidated as (25R)-3β-{O-β- d - xylopyranosyl -(1 → 2)-O-α- l - rhamnopyranosyl -(1 → 4)-O-[α- l - rhamnopyranosyl -(1 → 2)]-β- d - glucopyranosyloxy }-22αN- spirosol-5-ene and (25S)-3β-O-β- d - xylopyranosyl -(1 → 2)-O-α- l - rhamnopyranosyl -(1 → 4)-O-[α- l - rhamnopyranosyl -(1 → 2)]-β - d - glucopyranosyloxy }-22βN- spirosol-5-ene .

  • Steroid Alkaloid glycosides from solanum robustum
    Phytochemistry, 1995
    Co-Authors: Helmut Ripperger
    Abstract:

    Solamargine, solasonine, N-hydroxyrobustine and a new glycoAlkaloid, N-hydroxysolamargine, has been isolated from the leaves of Solanum robustum, the structure of which has been elucidated as (25R)-3beta-{O-alpha-L-rhamnopyranosyl-(1-->2)-O-[alpha-L- rhamnopyranosyl- (1-->4)]-beta-D-glucopyranosyloxy}-22alphaN- spirosol-5-en-N-ol.

  • solanum Alkaloids 128 Steroid Alkaloid glycosides from solanum robustum
    European Journal of Organic Chemistry, 1994
    Co-Authors: Helmut Ripperger, Andrea Porzel
    Abstract:

    β1-Solamargine and three new glycoAlkaloids, robustine, N-hydroxyrobustine, and 25-acetoxyrobustine, have been isolated from the roots of Solanum robustum, the structures of which have been elucidated as 3-O-{O-α-L-arabinopyranosyl-(13)-O-[α-L-rhamnopyranosyl-(12)]- O-[α-L-rhamnopyranosyl-(14)]-(β-D-glucopyranosyl}solasodine (3)), its N-hydroxy, and its 25-acetoxy derivative. These compounds have characteristic structures in comparison with the hitherto known Solanum glycoAlkaloids.

  • Anguivine and isoanguivine Steroid Alkaloid glycosides fromSolanum anguivi
    Phytochemistry, 1994
    Co-Authors: Helmut Ripperger, Uwe Himmelreich
    Abstract:

    Abstract In addition to solamargine, two new Steroid Alkaloid glycosides, anguivine and isoanguivine, have been isolated from the roots of Solanum anguivi ,

Klaus Schreiber - One of the best experts on this subject based on the ideXlab platform.

Takayuki Yonezawa - One of the best experts on this subject based on the ideXlab platform.

  • a Steroid Alkaloid derivative 02f04 upregulates thymic stromal lymphopoietin expression slowly and continuously through a novel gq 11 rock erk1 2 signaling pathway in mouse keratinocytes
    Cellular Signalling, 2019
    Co-Authors: Yan Weng, Ryosuke Segawa, Takahiro Moriya, Jingwen Wang, Zhifu Yang, Jialin Duan, Chao Guo, Ying Yin, Takayuki Yonezawa
    Abstract:

    Abstract Thymic stromal lymphopoietin (TSLP), a master switch of allergic inflammation, plays an important role in the pathogenesis of allergic diseases. Although many compounds upregulate TSLP expression in vivo or in vitro, most of them are pollutants or toxicants. In the previous study, for the first time, we found that a Steroid Alkaloid derivative 02F04, which has a unique skeletal structure compared with other TSLP-inducing chemicals, significantly induced TSLP production in mouse keratinocytes. However, it is not investigated thoroughly that how 02F04 produces TSLP and why. In this study, we did a detailed investigation on the inducible effect and underlying molecular mechanism of 02F04 on TSLP production. We found that the peak time of TSLP mRNA level induced by 02F04 at 48 h led to a slow and continuous TSLP production in PAM212 cells. Besides, 02F04-induced TSLP production was significantly suppressed by inhibitors of Rho-associated protein kinase (ROCK), guanine nucleotide-binding protein subunit alpha q/11 (Gq/11) and extracellular signal-regulated kinase 1/2 (ERK1/2) at not only protein but also mRNA levels, and by siRNA-mediated knockdown of Gq or G11. This suggested that ROCK, Gq/11 and ERK1/2 signaling pathways were involved in 02F04-induced TSLP production. Increase in the level of p-ERK1/2 induced by 02F04 was suppressed by both inhibitors of ROCK and Gq/11, indicating that ROCK and Gq/11 molecules were located at the upstream of ERK1/2 to regulate 02F04-induced TSLP production. Gq/11 was located at the upstream of ROCK because the specific Gq/11 inhibitor of YM-254890 significantly reduced 02F04-induced actin stress fiber formation. Taken together, 02F04 upregulates a slow and continuous TSLP production through a novel Gq/11-ROCK-ERK1/2 signaling pathway. The thorough understanding the effect and mechanism of 02F04 on TSLP production is expected to supply it as a novel TSLP-regulating compound and a potential new tool for investigating the role of TSLP in allergic disorders.

  • induction of thymic stromal lymphopoietin by a Steroid Alkaloid derivative in mouse keratinocytes
    International Immunopharmacology, 2018
    Co-Authors: Yan Weng, Natsumi Mizuno, Jiangxu Dong, Ryosuke Segawa, Takayuki Yonezawa, Byungyoon Cha, Jetae Woo, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
    Abstract:

    Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and exacerbating allergic diseases. Chemical compounds that induce TSLP production can enhance sensitization to antigens and exacerbate allergic inflammation. Hence, identifying such chemicals will be important to prevent an increase in allergic diseases. In the present study, we found, for the first time, that a Steroid Alkaloid derivative, code no. 02F04, concentration and time dependently induced mRNA expression and production of TSLP in a mouse keratinocyte cell line, PAM212. In particular, the activity of 02F04 was selective to TSLP. As an analogue of the liver X receptor (LXR) endogenous ligand, 02F04 rapidly increased ATP-binding cassette transporter A1 (ABCA1) expression by regulating the nuclear receptor of LXR. However, instead of being inhibited by the LXR antagonist, 02F04-induced TSLP production was delayed and markedly suppressed by inhibitors of phospholipase C (PLC), pan-protein kinase C (PKC), PKCδ, Rho-associated protein kinase (ROCK), extracellular signal-regulated kinase (ERK) 1/2, and IκΒ kinase 2 (IKK2). Treatment with 02F04 caused the formation of F-actin filaments surrounding the nucleus of PAM212 cells, which then disappeared following addition of ROCK inhibitor. 02F04 also induced phosphorylation of ERK1/2 from 2h after treatment, with a maximum at 24h, and increased nuclear factor-κB (NF-κB) promoter activity by 1.3-fold. Taken together, these results indicate that 02F04-induced TSLP production is regulated via distinct signal transduction pathways, including PLC, PKC, ROCK, ERK1/2, and NF-κB but not nuclear receptors. 02F04, with a unique skeletal structure in inducing TSLP production, can represent a potential new tool for investigating the role of TSLP in allergic diseases.

Noriyasu Hirasawa - One of the best experts on this subject based on the ideXlab platform.

  • induction of thymic stromal lymphopoietin by a Steroid Alkaloid derivative in mouse keratinocytes
    International Immunopharmacology, 2018
    Co-Authors: Yan Weng, Natsumi Mizuno, Jiangxu Dong, Ryosuke Segawa, Takayuki Yonezawa, Byungyoon Cha, Jetae Woo, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
    Abstract:

    Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and exacerbating allergic diseases. Chemical compounds that induce TSLP production can enhance sensitization to antigens and exacerbate allergic inflammation. Hence, identifying such chemicals will be important to prevent an increase in allergic diseases. In the present study, we found, for the first time, that a Steroid Alkaloid derivative, code no. 02F04, concentration and time dependently induced mRNA expression and production of TSLP in a mouse keratinocyte cell line, PAM212. In particular, the activity of 02F04 was selective to TSLP. As an analogue of the liver X receptor (LXR) endogenous ligand, 02F04 rapidly increased ATP-binding cassette transporter A1 (ABCA1) expression by regulating the nuclear receptor of LXR. However, instead of being inhibited by the LXR antagonist, 02F04-induced TSLP production was delayed and markedly suppressed by inhibitors of phospholipase C (PLC), pan-protein kinase C (PKC), PKCδ, Rho-associated protein kinase (ROCK), extracellular signal-regulated kinase (ERK) 1/2, and IκΒ kinase 2 (IKK2). Treatment with 02F04 caused the formation of F-actin filaments surrounding the nucleus of PAM212 cells, which then disappeared following addition of ROCK inhibitor. 02F04 also induced phosphorylation of ERK1/2 from 2h after treatment, with a maximum at 24h, and increased nuclear factor-κB (NF-κB) promoter activity by 1.3-fold. Taken together, these results indicate that 02F04-induced TSLP production is regulated via distinct signal transduction pathways, including PLC, PKC, ROCK, ERK1/2, and NF-κB but not nuclear receptors. 02F04, with a unique skeletal structure in inducing TSLP production, can represent a potential new tool for investigating the role of TSLP in allergic diseases.