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Jenkun Lin - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of 12 o tetradecanoylphorbol 13 acetate induced inflammatory Skin Edema and ornithine decarboxylase activity by theaflavin 3 3 digallate in mouse
    Nutrition and Cancer, 2002
    Co-Authors: Yu Chih Liang, De Cheng Tsai, Shoeiyn Linshiau, Chieh Fu Chen, Jenkun Lin
    Abstract:

    Among black tea polyphenols, theaflavins were generally considered to be the most effective in cancer chemoprevention. In this study, we examined the inhibitory effects of black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate and theaflavin-3′-gallate, theaflavin-3,3′-digallate (TF-3), and the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Edema and ornithine decarboxylase (ODC) activity. Topical application of these polyphenols onto the mouse resulted in inhibition of TPA-induced ear Edema and Skin epidermal ODC activity. The inhibitory order was as follows: TF-3 > TF-2 ≃ EGCG > TF-1. Western and Northern blots indicated that TF-3 significantly reduced the protein and mRNA levels of ODC in TPA-treated mouse Skin and NIH 3T3 cells, whereas EGCG showed less activity. EGCG and TF-3 were able to inhibit the ODC enzyme activity in vitro. Furthermore, TF-3 also significantly reduced the basal promoter activ...

  • inhibition of 12 o tetradecanoylphorbol 13 acetate induced inflammatory Skin Edema and ornithine decarboxylase activity by theaflavin 3 3 digallate in mouse
    Nutrition and Cancer, 2002
    Co-Authors: Yu Chih Liang, De Cheng Tsai, Shoeiyn Linshiau, Chieh Fu Chen, Jenkun Lin
    Abstract:

    Among black tea polyphenols, theaflavins were generally considered to be the most effective in cancer chemoprevention. In this study, we examined the inhibitory effects of black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), and the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Edema and ornithine decarboxylase (ODC) activity. Topical application of these polyphenols onto the mouse resulted in inhibition of TPA-induced ear Edema and Skin epidermal ODC activity. The inhibitory order was as follows: TF-3 > TF-2 approximately equal to EGCG > TF-1. Western and Northern blots indicated that TF-3 significantly reduced the protein and mRNA levels of ODC in TPA-treated mouse Skin and NIH 3T3 cells, whereas EGCG showed less activity. EGCG and TF-3 were able to inhibit the ODC enzyme activity in vitro. Furthermore, TF-3 also significantly reduced the basal promoter activity of the ODC gene in NIH 3T3 cells that were transiently transfected with ODC reporter plasmid. These results suggested that TF-3 was a potential inhibitor of ODC activity and TPA-induced Edema and might be effective in cancer chemoprevention.

Masao Murakawa - One of the best experts on this subject based on the ideXlab platform.

  • asb16165 a phosphodiesterase 7a inhibitor reduces cutaneous tnf α level and ameliorates Skin Edema in phorbol ester 12 o tetradecanoylphorbol 13 acetate induced Skin inflammation model in mice
    European Journal of Pharmacology, 2009
    Co-Authors: Kumiko Kadoshimayamaoka, Megumi Goto, Masao Murakawa, Ryosuke Yoshioka, Yoshitaka Tanaka, Hidekazu Inoue, Hidenobu Murafuji, Satomi Kanki, Yasuhiro Hayashi, Kazuhiro Nagahira
    Abstract:

    Abstract Possible role of phosphodiesterase 7A (PDE7A) in Skin inflammation was examined using ASB16165, a specific inhibitor for PDE7A. Epicutaneous application of phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear resulted in induction of Skin Edema, and topical treatment with ASB16165 inhibited the induction of Skin Edema in a dose-dependent manner. The TPA challenge also increased the level of TNF-α at the application site, and the ASB16165 treatment reduced the TNF-α level in the Skin. In addition, ASB16165 suppressed the production of TNF-α by human keratinocytes stimulated in vitro with TPA and calcium ionophore. Forskolin, an activator of adenylyl cyclase, as well as dibutyryl cAMP also showed inhibitory effect on the TNF-α production in the cells, suggesting involvement of cAMP in TNF-α generation. These results demonstrate that PDE7A might regulate TNF-α production in keratinocytes in a cAMP-dependent fashion. As immunostaining analysis revealed that PDE7A is expressed in the epidermis and TNF-α is known to contribute to the TPA-induced Edema, it is possible that the inhibitory effect of ASB16165 on Skin Edema in mouse TPA-induced dermatitis model is mediated by suppression of TNF-α production. This is the first report suggesting the association of PDE7A with the function of keratinocytes. ASB16165 will be useful as an agent for Skin inflammation in which TNF-α plays a pathogenic role ( e.g. psoriasis).

  • involvement of tumor necrosis factor tnf α in phorbol ester 12 o tetradecanoylphorbol 13 acetate tpa induced Skin Edema in mice
    Biochemical Pharmacology, 2006
    Co-Authors: Masao Murakawa, Yoshitaka Tanaka, Kumiko Yamaoka, Yoshiaki Fukuda
    Abstract:

    Abstract Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear induced a prolonged Skin inflammation. Histological analysis revealed that the early stage (∼3 h) and later stage (6–24 h) of the Skin reaction are characterized by dermal Edema and cell accumulation, respectively. Topical application with TPA also induced increase in the level of TNF-α and prostagrandin E2 (PGE2) at the application site. The increase of TNF-α was transient with a peak at ∼5 h, followed by a gradual elevation of PGE2 level in the Skin. An in vitro study with human keratinocytes as well as immunohistochemical analysis suggested that TNF-α induction in the Skin might be produced by epidermis treated with TPA. Administration of a cyclooxygenase inhibitor indomethacin inhibited the later stage of the TPA-induced Edema. In contrast, TNF-α antagonist etanercept inhibited exclusively the early stage of the reaction. Taken together, these data demonstrate that the prolongation of the Skin inflammation induced by TPA may be due to the sequential production of proinflammatory mediators such as eicosanoids and cytokines, and show for the first time the importance of TNF-α in the TPA-induced dermatitis especially at the stage where dermal Edema is significant.

  • involvement of tumor necrosis factor tnf α in phorbol ester 12 o tetradecanoylphorbol 13 acetate tpa induced Skin Edema in mice
    Biochemical Pharmacology, 2006
    Co-Authors: Masao Murakawa, Yoshitaka Tanaka, Kumiko Yamaoka, Yoshiaki Fukuda
    Abstract:

    Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear induced a prolonged Skin inflammation. Histological analysis revealed that the early stage (approximately 3 h) and later stage (6-24 h) of the Skin reaction are characterized by dermal Edema and cell accumulation, respectively. Topical application with TPA also induced increase in the level of TNF-alpha and prostagrandin E2 (PGE2) at the application site. The increase of TNF-alpha was transient with a peak at approximately 5 h, followed by a gradual elevation of PGE2 level in the Skin. An in vitro study with human keratinocytes as well as immunohistochemical analysis suggested that TNF-alpha induction in the Skin might be produced by epidermis treated with TPA. Administration of a cyclooxygenase inhibitor indomethacin inhibited the later stage of the TPA-induced Edema. In contrast, TNF-alpha antagonist etanercept inhibited exclusively the early stage of the reaction. Taken together, these data demonstrate that the prolongation of the Skin inflammation induced by TPA may be due to the sequential production of proinflammatory mediators such as eicosanoids and cytokines, and show for the first time the importance of TNF-alpha in the TPA-induced dermatitis especially at the stage where dermal Edema is significant.

Yoshiaki Fukuda - One of the best experts on this subject based on the ideXlab platform.

  • involvement of tumor necrosis factor tnf α in phorbol ester 12 o tetradecanoylphorbol 13 acetate tpa induced Skin Edema in mice
    Biochemical Pharmacology, 2006
    Co-Authors: Masao Murakawa, Yoshitaka Tanaka, Kumiko Yamaoka, Yoshiaki Fukuda
    Abstract:

    Abstract Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear induced a prolonged Skin inflammation. Histological analysis revealed that the early stage (∼3 h) and later stage (6–24 h) of the Skin reaction are characterized by dermal Edema and cell accumulation, respectively. Topical application with TPA also induced increase in the level of TNF-α and prostagrandin E2 (PGE2) at the application site. The increase of TNF-α was transient with a peak at ∼5 h, followed by a gradual elevation of PGE2 level in the Skin. An in vitro study with human keratinocytes as well as immunohistochemical analysis suggested that TNF-α induction in the Skin might be produced by epidermis treated with TPA. Administration of a cyclooxygenase inhibitor indomethacin inhibited the later stage of the TPA-induced Edema. In contrast, TNF-α antagonist etanercept inhibited exclusively the early stage of the reaction. Taken together, these data demonstrate that the prolongation of the Skin inflammation induced by TPA may be due to the sequential production of proinflammatory mediators such as eicosanoids and cytokines, and show for the first time the importance of TNF-α in the TPA-induced dermatitis especially at the stage where dermal Edema is significant.

  • involvement of tumor necrosis factor tnf α in phorbol ester 12 o tetradecanoylphorbol 13 acetate tpa induced Skin Edema in mice
    Biochemical Pharmacology, 2006
    Co-Authors: Masao Murakawa, Yoshitaka Tanaka, Kumiko Yamaoka, Yoshiaki Fukuda
    Abstract:

    Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear induced a prolonged Skin inflammation. Histological analysis revealed that the early stage (approximately 3 h) and later stage (6-24 h) of the Skin reaction are characterized by dermal Edema and cell accumulation, respectively. Topical application with TPA also induced increase in the level of TNF-alpha and prostagrandin E2 (PGE2) at the application site. The increase of TNF-alpha was transient with a peak at approximately 5 h, followed by a gradual elevation of PGE2 level in the Skin. An in vitro study with human keratinocytes as well as immunohistochemical analysis suggested that TNF-alpha induction in the Skin might be produced by epidermis treated with TPA. Administration of a cyclooxygenase inhibitor indomethacin inhibited the later stage of the TPA-induced Edema. In contrast, TNF-alpha antagonist etanercept inhibited exclusively the early stage of the reaction. Taken together, these data demonstrate that the prolongation of the Skin inflammation induced by TPA may be due to the sequential production of proinflammatory mediators such as eicosanoids and cytokines, and show for the first time the importance of TNF-alpha in the TPA-induced dermatitis especially at the stage where dermal Edema is significant.

Hasan Mukhtar - One of the best experts on this subject based on the ideXlab platform.

  • oral feeding of pomegranate fruit extract inhibits early biomarkers of uvb radiation induced carcinogenesis in skh 1 hairless mouse epidermis
    Photochemistry and Photobiology, 2010
    Co-Authors: Farrukh Afaq, Naghma Khan, Deeba N Syed, Hasan Mukhtar
    Abstract:

    Pomegranate from the plant Punica granatum L. possesses strong antioxidant and anti-inflammatory properties. Recently, we have demonstrated that treatment of normal human epidermal keratinocytes with pomegranate fruit extract (PFE) inhibited UVB-mediated activation of nuclear factor kappa B (NF-κB) and mitogen activated protein kinases pathways. Here, we evaluated the effect of PFE on early biomarkers of photocarcinogenesis employing SKH-1 hairless mice. PFE was provided in drinking water (0.2%, wt/vol) to SKH-1 hairless mice for 14 days before a single UVB (180 mJ cm -2 ) irradiation. We found that oral feeding of PFE inhibited UVB-induced: (1) Skin Edema; (2) hyperplasia; (3) infiltration of leukocytes; (4) lipid peroxidation; (5) hydrogen peroxide generation; (6) ornithine decarboxylase (ODC) activity; and (7) ODC, cyclooxygenase-2 and proliferating cell nuclear antigen protein expression. Oral feeding of PFE enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Importantly, PFE treatment further enhanced UVB-mediated increase in tumor suppressor p53 and cyclin kinase inhibitor p21. Furthermore, oral feeding of PFE inhibited UVB-mediated: (1) nuclear translocation of NF-κB; (2) activation of IKKα; and (3) phosphorylation and degradation of IκBα. Taken together, we provide evidence that oral feeding of PFE to mice affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential.

  • guggulsterone modulates mapk and nf κb pathways and inhibits Skin tumorigenesis in sencar mice
    Carcinogenesis, 2008
    Co-Authors: Sami Sarfaraz, Deeba N Syed, Farrukh Afaq, Imtiaz A Siddiqui, Hasan Mukhtar
    Abstract:

    Guggulsterone (GUG), a resin of the Commiphora mukul tree, has been used in ayurvedic medicine for centuries to treat a variety of ailments. Recent studies have suggested that GUG may also possess anticancer effects. In the present study, we show that GUG possesses antitumor-promoting effects in SENCAR mouse Skin tumorigenesis model. We first determined the effect of topical application of GUG to mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced conventional markers and other novel markers of Skin tumor promotion. We found that topical application of GUG (1.6 micromol per mouse) 30 min prior to TPA (3.2 nmol per mouse) application onto the Skin of mice afforded significant inhibition against TPA-mediated increase in Skin Edema and hyperplasia. Topical application of GUG was also found to result in substantial inhibition against TPA-induced epidermal (i) ornithine decarboxylase (ODC) activity; (ii) ODC, cyclooxygenase-2 and inducible nitric oxide synthase protein expressions; (iii) phosphorylation of extracellular signal-regulated kinase 1/2, c-jun N-terminal kinases and p38; (iv) activation of NF-kappaB/p65 and IKK alpha/beta and (v) phosphorylation and degradation of I kappaB alpha. We next assessed the effect of topically applied GUG on TPA-induced Skin tumor promotion in 7,12-dimethyl benz[a]anthracene-initiated mice. Compared with non-GUG-pretreated mice, animals pretreated with GUG showed significantly reduced tumor incidence, lower tumor body burden and a significant delay in the latency period for tumor appearance from 5 to 11 weeks. These results provide the first evidence that GUG possesses anti-Skin tumor-promoting effects in SENCAR mice and inhibits conventional as well as novel biomarkers of tumor promotion. In summary, GUG could be useful for delaying tumor growth in humans.

  • protective effect of sanguinarine on ultraviolet b mediated damages in skh 1 hairless mouse Skin implications for prevention of Skin cancer
    Photochemistry and Photobiology, 2007
    Co-Authors: Haseeb Ahsan, Hasan Mukhtar, Farrukh Afaq, Shannon Reaganshaw, David M Eggert, Thomas C Tan, Nihal Ahmad
    Abstract:

    Excessive exposure of solar ultraviolet (UV) radiation, particularly its UVB component (280-320 nm), to human Skin is the major cause of Skin cancers. UV exposure also leads to the development of precancerous conditions such as actinic keratosis and elicits a variety of other adverse effects such as sunburn, inflammation, hyperplasia, immunosuppression and Skin aging. Therefore, there is a need to intensify our efforts towards the development of novel mechanism-based approaches/agents for the protection of UVB-mediated damages. Chemoprevention is being investigated as a potential approach for the management of UV damages including Skin cancer. We have earlier shown that sanguinarine, a benzophenanthridine alkaloid, inhibits UVB exposure-mediated damages in HaCaT keratinocytes. In this study, to determine the relevance of our in vitro findings to in vivo situations, we assessed the effects of sanguinarine on UVB-mediated damages in SKH-1 hairless mice. Our data demonstrated that a topical application of sanguinarine (5 micromol 0.3 mL(-1) ethanol per mouse), either as a pretreatment (30 min prior to UVB) or posttreatment (5 min after UVB), resulted in a significant decrease in UVB-mediated increases in Skin Edema, Skin hyperplasia and infiltration of leukocytes. Further, sanguinarine treatments (pre and post) also resulted in a significant decrease in UVB mediated (1) generation of H2O2 and (2) increases in the protein levels of markers of tumor promotion/proliferation viz. ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA) and Kiel antigen-67. Based on this data, we suggest that sanguinarine could be developed as an agent for the management of conditions elicited by UV exposure including Skin cancer. However, further detailed studies are needed to support this suggestion.

  • anthocyanin and hydrolyzable tannin rich pomegranate fruit extract modulates mapk and nf κb pathways and inhibits Skin tumorigenesis in cd 1 mice
    International Journal of Cancer, 2005
    Co-Authors: Farrukh Afaq, Mohammad Saleem, Christian G Krueger, Jess D Reed, Hasan Mukhtar
    Abstract:

    Chemoprevention has come of age as an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable of intervening at more than one critical pathway in the carcinogenesis process will have greater advantage over other single-target agents. Pomegranate fruit extract (PFE) derived from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. Pomegranate fruit was extracted with acetone and analyzed based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and found to contain anthocyanins, ellagitannins and hydrolyzable tannins. We evaluated whether PFE possesses antitumor-promoting effects. We first determined the effect of topical application of PFE to CD-1 mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)induced conventional markers and other novel markers of Skin tumor promotion. We found that topical application of PFE (2 mg/mouse) 30 min prior to TPA (3.2 nmole/mouse) application on mouse Skin afforded significant inhibition, in a time-dependent manner, against TPA-mediated increase in Skin Edema and hyperplasia, epidermal ornithine decarboxylase (ODC) activity and protein expression of ODC and cyclooxygenase-2. We also found that topical application of PFE resulted in inhibition of TPA-induced phosphorylation of ERK1/2, p38 and JNK1/2, as well as activation of NF-! B and IKK" and phosphorylation and degradation of I! B" . We next assessed the effect of Skin application of PFE on TPA-induced Skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated CD-1 mouse. The animals pretreated with PFE showed substantially reduced tumor incidence and lower tumor body burden when assessed as total number of tumors per group, percent of mice with tumors and number of tumors per animal as compared to animals that did not receive PFE. In TPA-treated group, 100% of the mice developed tumors at 16 weeks on test, whereas at this time in PFE-treated group, only 30% mice exhibited tumors. Skin application of PFE prior to TPA application also resulted in a significant delay in latency period from 9 to 14 weeks and afforded protection when tumor data were considered in terms of tumor incidence and tumor multiplicity. The results of our study provide clear evidence that PFE possesses antiSkintumor-promoting effects in CD-1 mouse. Because PFE is capable of inhibiting conventional as well as novel biomarkers of TPAinduced tumor promotion, it may possess chemopreventive activity in a wide range of tumor models. Thus, an in-depth study to define active agent(s) in PFE capable of affording antitumorpromoting effect is warranted.

  • lupeol modulates nf κb and pi3k akt pathways and inhibits Skin cancer in cd 1 mice
    Oncogene, 2004
    Co-Authors: Mohammad Saleem, Vaqar M. Adhami, Farrukh Afaq, Hasan Mukhtar
    Abstract:

    Chemoprevention has become an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable for inhibition of promotion stage of tumorigenesis with the ability to intervene at several critical pathways in the tumorigenesis process will have greater advantage over other single-target agents. Lupeol, a triterpene, is the principal constituent of common fruit plants such as olive, mango, fig and medicinal herbs that have been used to treat Skin aliments. Lupeol has been reported to possess a wide range of medicinal properties that include strong antioxidant, antimutagenic, anti-inflammatory and antiarthritic effects. In the present study, we show that Lupeol possesses antitumor-promoting effects in a mouse Skin tumorigenesis model. We first determined the effect of topical application of Lupeol to CD-1 mouse against 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced conventional markers and other novel markers of Skin tumor promotion. We found that topical application of Lupeol (1–2 mg/mouse) 30 min prior to TPA (3.2 nmol/mouse) application onto the Skin of CD-1 mice afforded significant inhibition, in a time- and dose-dependent manner, against TPA-mediated increase in (i) Skin Edema and hyperplasia, (ii) epidermal ornithine decarboxylase (ODC) activity, and (iii) protein expression of ODC, cyclo-oxygenase-2 and nitric oxide synthase. As of the role of nuclear factor kappa B (NF-κB) and phosphatidyl inositol 3-kinase (PI3K)/Akt signaling in tumor promotion, we next determined the effect of topical application of Lupeol to mouse Skin against these signaling pathways. We found that Lupeol treatment to mouse Skin resulted in the inhibition of TPA-induced (i) activation of PI3K, (ii) phosphorylation of Akt at Thr308, (iii) activation of NF-κB and IKKα, and (iv) degradation and phosphorylation of IκBα. The animals pretreated with Lupeol showed significantly reduced tumor incidence, lower tumor body burden and a significant delay in the latency period for tumor appearance. At the termination of the experiment at 28 weeks, 100% of the animals in TPA-treated group exhibited seven to eight tumors/mouse, whereas only 53% of the mice receiving Lupeol prior to TPA treatment exhibited one to three tumors/mouse. These results for the first time provide evidence that Lupeol possesses antiSkin tumor-promoting effects in CD-1 mouse and inhibits conventional as well as novel biomarkers of tumor promotion. We suggest that Lupeol is an attractive antitumor-promoting agent that must be evaluated in tumor models other than Skin carcinogenesis.

Yoshitaka Tanaka - One of the best experts on this subject based on the ideXlab platform.

  • asb16165 a phosphodiesterase 7a inhibitor reduces cutaneous tnf α level and ameliorates Skin Edema in phorbol ester 12 o tetradecanoylphorbol 13 acetate induced Skin inflammation model in mice
    European Journal of Pharmacology, 2009
    Co-Authors: Kumiko Kadoshimayamaoka, Megumi Goto, Masao Murakawa, Ryosuke Yoshioka, Yoshitaka Tanaka, Hidekazu Inoue, Hidenobu Murafuji, Satomi Kanki, Yasuhiro Hayashi, Kazuhiro Nagahira
    Abstract:

    Abstract Possible role of phosphodiesterase 7A (PDE7A) in Skin inflammation was examined using ASB16165, a specific inhibitor for PDE7A. Epicutaneous application of phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear resulted in induction of Skin Edema, and topical treatment with ASB16165 inhibited the induction of Skin Edema in a dose-dependent manner. The TPA challenge also increased the level of TNF-α at the application site, and the ASB16165 treatment reduced the TNF-α level in the Skin. In addition, ASB16165 suppressed the production of TNF-α by human keratinocytes stimulated in vitro with TPA and calcium ionophore. Forskolin, an activator of adenylyl cyclase, as well as dibutyryl cAMP also showed inhibitory effect on the TNF-α production in the cells, suggesting involvement of cAMP in TNF-α generation. These results demonstrate that PDE7A might regulate TNF-α production in keratinocytes in a cAMP-dependent fashion. As immunostaining analysis revealed that PDE7A is expressed in the epidermis and TNF-α is known to contribute to the TPA-induced Edema, it is possible that the inhibitory effect of ASB16165 on Skin Edema in mouse TPA-induced dermatitis model is mediated by suppression of TNF-α production. This is the first report suggesting the association of PDE7A with the function of keratinocytes. ASB16165 will be useful as an agent for Skin inflammation in which TNF-α plays a pathogenic role ( e.g. psoriasis).

  • involvement of tumor necrosis factor tnf α in phorbol ester 12 o tetradecanoylphorbol 13 acetate tpa induced Skin Edema in mice
    Biochemical Pharmacology, 2006
    Co-Authors: Masao Murakawa, Yoshitaka Tanaka, Kumiko Yamaoka, Yoshiaki Fukuda
    Abstract:

    Abstract Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear induced a prolonged Skin inflammation. Histological analysis revealed that the early stage (∼3 h) and later stage (6–24 h) of the Skin reaction are characterized by dermal Edema and cell accumulation, respectively. Topical application with TPA also induced increase in the level of TNF-α and prostagrandin E2 (PGE2) at the application site. The increase of TNF-α was transient with a peak at ∼5 h, followed by a gradual elevation of PGE2 level in the Skin. An in vitro study with human keratinocytes as well as immunohistochemical analysis suggested that TNF-α induction in the Skin might be produced by epidermis treated with TPA. Administration of a cyclooxygenase inhibitor indomethacin inhibited the later stage of the TPA-induced Edema. In contrast, TNF-α antagonist etanercept inhibited exclusively the early stage of the reaction. Taken together, these data demonstrate that the prolongation of the Skin inflammation induced by TPA may be due to the sequential production of proinflammatory mediators such as eicosanoids and cytokines, and show for the first time the importance of TNF-α in the TPA-induced dermatitis especially at the stage where dermal Edema is significant.

  • involvement of tumor necrosis factor tnf α in phorbol ester 12 o tetradecanoylphorbol 13 acetate tpa induced Skin Edema in mice
    Biochemical Pharmacology, 2006
    Co-Authors: Masao Murakawa, Yoshitaka Tanaka, Kumiko Yamaoka, Yoshiaki Fukuda
    Abstract:

    Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear induced a prolonged Skin inflammation. Histological analysis revealed that the early stage (approximately 3 h) and later stage (6-24 h) of the Skin reaction are characterized by dermal Edema and cell accumulation, respectively. Topical application with TPA also induced increase in the level of TNF-alpha and prostagrandin E2 (PGE2) at the application site. The increase of TNF-alpha was transient with a peak at approximately 5 h, followed by a gradual elevation of PGE2 level in the Skin. An in vitro study with human keratinocytes as well as immunohistochemical analysis suggested that TNF-alpha induction in the Skin might be produced by epidermis treated with TPA. Administration of a cyclooxygenase inhibitor indomethacin inhibited the later stage of the TPA-induced Edema. In contrast, TNF-alpha antagonist etanercept inhibited exclusively the early stage of the reaction. Taken together, these data demonstrate that the prolongation of the Skin inflammation induced by TPA may be due to the sequential production of proinflammatory mediators such as eicosanoids and cytokines, and show for the first time the importance of TNF-alpha in the TPA-induced dermatitis especially at the stage where dermal Edema is significant.