Skip to main content
Erschienen in: Inflammation 2/2016

21.01.2016 | ORIGINAL ARTICLE

Esculetin Attenuates Th2 and Th17 Responses in an Ovalbumin-Induced Asthmatic Mouse Model

verfasst von: Long Hongyan

Erschienen in: Inflammation | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

The purpose of the current study was to investigate the anti-asthmatic effect of esculetin (ES) and explore its potential mechanism with a mouse model of allergic asthma. A total number of 50 mice were randomly assigned to five groups: control, model, dexamethasone (Dex, 2 mg/kg), and ES (20 mg/kg, 40 mg/kg). Mouse asthma model was developed with the sensitization and challenge of ovalbumin (OVA). The levels of IgE in serum, eosinophilia infiltration, Th2/Th17 cytokines, Th17 cell frequency, histological condition, and the protein expressions of RORγt, GATA3 were detected. Our study demonstrated that ES inhibited, OVA-induced eosinophil count, interleukin-4 (IL-4), IL-5, IL-13, and IL-17A levels were recovered in bronchoalveolar lavage fluid. Flow cytometry (FCM) studies revealed that ES substantially inhibited Th17 cells’ percentage. Western blot study also indicated that ES downregulated RORγt and GATA3 expressions. Meanwhile, ES had beneficial effects on the histological alteration. These findings suggested that ES might effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.
Literatur
1.
Zurück zum Zitat Ogulur, I., G. Gurhan, F.E. Kombak, D. Filinte, I. Barlan, and T. Akkoc. 2014. Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma. International immunopharmacology 22: 31–40.CrossRefPubMed Ogulur, I., G. Gurhan, F.E. Kombak, D. Filinte, I. Barlan, and T. Akkoc. 2014. Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma. International immunopharmacology 22: 31–40.CrossRefPubMed
2.
Zurück zum Zitat Sozanska, B., M. Blaszczyk, N. Pearce, and P. Cullinan. 2014. Atopy and allergic respiratory disease in rural Poland before and after accession to the European Union. The Journal of allergy and clinical immunology 133: 1347–53.CrossRefPubMed Sozanska, B., M. Blaszczyk, N. Pearce, and P. Cullinan. 2014. Atopy and allergic respiratory disease in rural Poland before and after accession to the European Union. The Journal of allergy and clinical immunology 133: 1347–53.CrossRefPubMed
3.
Zurück zum Zitat Wang, J., T. Zhang, C. Ma, and S. Wang. 2015. Puerarin attenuates airway inflammation by regulation of eotaxin-3. Immunology letters 163: 173–8.CrossRefPubMed Wang, J., T. Zhang, C. Ma, and S. Wang. 2015. Puerarin attenuates airway inflammation by regulation of eotaxin-3. Immunology letters 163: 173–8.CrossRefPubMed
4.
Zurück zum Zitat Shieh, Y.H., H.M. Huang, C.C. Wang, C.C. Lee, C.K. Fan, and Y.L. Lee. 2015. Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice. International immunopharmacology 24: 383–91.CrossRefPubMed Shieh, Y.H., H.M. Huang, C.C. Wang, C.C. Lee, C.K. Fan, and Y.L. Lee. 2015. Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice. International immunopharmacology 24: 383–91.CrossRefPubMed
5.
Zurück zum Zitat Carsin, A., J. Bienvenu, Y. Pacheco, and G. Devouassoux. 2012. Physiopathology of aspirin intolerant asthma. Revue des maladies respiratoires 29: 118–27.CrossRefPubMed Carsin, A., J. Bienvenu, Y. Pacheco, and G. Devouassoux. 2012. Physiopathology of aspirin intolerant asthma. Revue des maladies respiratoires 29: 118–27.CrossRefPubMed
6.
Zurück zum Zitat Tianzhu, Z., Y. Shihai, and D. Juan. 2015. The effects of cordycepin on ovalbumin-induced allergic inflammation by strengthening Treg response and suppressing Th17 responses in ovalbumin-sensitized mice. Inflammation 38: 1036–43.CrossRefPubMed Tianzhu, Z., Y. Shihai, and D. Juan. 2015. The effects of cordycepin on ovalbumin-induced allergic inflammation by strengthening Treg response and suppressing Th17 responses in ovalbumin-sensitized mice. Inflammation 38: 1036–43.CrossRefPubMed
7.
Zurück zum Zitat Chen, T., J. Gao, P. Xiang, Y. Chen, J. Ji, P. Xie, et al. 2015. Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance. International immunopharmacology 26: 338–348.CrossRefPubMed Chen, T., J. Gao, P. Xiang, Y. Chen, J. Ji, P. Xie, et al. 2015. Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance. International immunopharmacology 26: 338–348.CrossRefPubMed
8.
Zurück zum Zitat Kaur, M., S. Reynolds, L.J. Smyth, K. Simpson, S. Hall, and D. Singh. 2014. The effects of corticosteroids on cytokine production from asthma lung lymphocytes. International immunopharmacology 23: 581–4.CrossRefPubMed Kaur, M., S. Reynolds, L.J. Smyth, K. Simpson, S. Hall, and D. Singh. 2014. The effects of corticosteroids on cytokine production from asthma lung lymphocytes. International immunopharmacology 23: 581–4.CrossRefPubMed
9.
Zurück zum Zitat Kim, S.H., J.H. Hong, and Y.C. Lee. 2014. Oleanolic acid suppresses ovalbumin-induced airway inflammation and Th2-mediated allergic asthma by modulating the transcription factors T-bet, GATA-3, RORgammat and Foxp3 in asthmatic mice. International immunopharmacology 18: 311–24.CrossRefPubMed Kim, S.H., J.H. Hong, and Y.C. Lee. 2014. Oleanolic acid suppresses ovalbumin-induced airway inflammation and Th2-mediated allergic asthma by modulating the transcription factors T-bet, GATA-3, RORgammat and Foxp3 in asthmatic mice. International immunopharmacology 18: 311–24.CrossRefPubMed
10.
Zurück zum Zitat Wakashin, H., K. Hirose, Y. Maezawa, S. Kagami, A. Suto, N. Watanabe, et al. 2008. IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice. American journal of respiratory and critical care medicine 178: 1023–32.CrossRefPubMed Wakashin, H., K. Hirose, Y. Maezawa, S. Kagami, A. Suto, N. Watanabe, et al. 2008. IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice. American journal of respiratory and critical care medicine 178: 1023–32.CrossRefPubMed
11.
Zurück zum Zitat Liu, Y.M., Y. Chen, J.Z. Li, and J.P. Gong. 2014. Up-regulation of Galectin-9 in vivo results in immunosuppressive effects and prolongs survival of liver allograft in rats. Immunology letters 162: 217–22.CrossRefPubMed Liu, Y.M., Y. Chen, J.Z. Li, and J.P. Gong. 2014. Up-regulation of Galectin-9 in vivo results in immunosuppressive effects and prolongs survival of liver allograft in rats. Immunology letters 162: 217–22.CrossRefPubMed
12.
Zurück zum Zitat Chen T, Ma Z, Zhu L, Jiang W, Wei T, Zhou R, et al. 2015. Suppressing receptor-interacting protein 140: a new sight for salidroside to treat cerebral ischemia. Molecular neurobiology. doi:10.1007/s12035-015-9521-7. Chen T, Ma Z, Zhu L, Jiang W, Wei T, Zhou R, et al. 2015. Suppressing receptor-interacting protein 140: a new sight for salidroside to treat cerebral ischemia. Molecular neurobiology. doi:10.​1007/​s12035-015-9521-7.
13.
Zurück zum Zitat Chen T, Wang R, Jiang W, Wang H, Xu A, Lu G, et al. 2015. Protective effect of astragaloside IV against paraquat-induced lung injury in mice by suppressing rho signaling. Inflammation. doi: 10.1007/s10753-015-0272-4. Chen T, Wang R, Jiang W, Wang H, Xu A, Lu G, et al. 2015. Protective effect of astragaloside IV against paraquat-induced lung injury in mice by suppressing rho signaling. Inflammation. doi: 10.​1007/​s10753-015-0272-4.
14.
Zurück zum Zitat Kim, A.D., X. Han, M.J. Piao, S.R. Hewage, C.L. Hyun, S.J. Cho, et al. 2015. Esculetin induces death of human colon cancer cells via the reactive oxygen species-mediated mitochondrial apoptosis pathway. Environmental toxicology and pharmacology 39: 982–9.CrossRefPubMed Kim, A.D., X. Han, M.J. Piao, S.R. Hewage, C.L. Hyun, S.J. Cho, et al. 2015. Esculetin induces death of human colon cancer cells via the reactive oxygen species-mediated mitochondrial apoptosis pathway. Environmental toxicology and pharmacology 39: 982–9.CrossRefPubMed
15.
Zurück zum Zitat Hong, S.H., H.K. Jeong, M.H. Han, C. Park, and Y.H. Choi. 2014. Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-kappaB translocation in RAW 264.7 macrophages. Molecular medicine reports 10: 3241–6.PubMed Hong, S.H., H.K. Jeong, M.H. Han, C. Park, and Y.H. Choi. 2014. Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-kappaB translocation in RAW 264.7 macrophages. Molecular medicine reports 10: 3241–6.PubMed
16.
Zurück zum Zitat Pan, H., B.H. Wang, W. Lv, Y. Jiang, and L. He. 2015. Esculetin induces apoptosis in human gastric cancer cells through a cyclophilin D-mediated mitochondrial permeability transition pore associated with ROS. Chemico-biological interactions 242: 51–60.CrossRefPubMed Pan, H., B.H. Wang, W. Lv, Y. Jiang, and L. He. 2015. Esculetin induces apoptosis in human gastric cancer cells through a cyclophilin D-mediated mitochondrial permeability transition pore associated with ROS. Chemico-biological interactions 242: 51–60.CrossRefPubMed
17.
Zurück zum Zitat Rzodkiewicz, P., E. Gasinska, S. Maslinski, and M. Bujalska-Zadrozny. 2015. Antinociceptive properties of esculetin in non-inflammatory and inflammatory models of pain in rats. Clinical and experimental pharmacology & physiology 42: 213–9.CrossRef Rzodkiewicz, P., E. Gasinska, S. Maslinski, and M. Bujalska-Zadrozny. 2015. Antinociceptive properties of esculetin in non-inflammatory and inflammatory models of pain in rats. Clinical and experimental pharmacology & physiology 42: 213–9.CrossRef
18.
Zurück zum Zitat Chen, T., Q. Guo, H. Wang, H. Zhang, C. Wang, P. Zhang, et al. 2015. Effects of esculetin on lipopolysaccharide (LPS)-induced acute lung injury via regulation of RhoA/Rho kinase/NF-κB pathways in vivo and in vitro. Free Radic Res 49: 1459–68.CrossRefPubMed Chen, T., Q. Guo, H. Wang, H. Zhang, C. Wang, P. Zhang, et al. 2015. Effects of esculetin on lipopolysaccharide (LPS)-induced acute lung injury via regulation of RhoA/Rho kinase/NF-κB pathways in vivo and in vitro. Free Radic Res 49: 1459–68.CrossRefPubMed
19.
Zurück zum Zitat Chen, T., Y. Mou, J. Tan, L. Wei, Y. Qiao, T. Wei, et al. 2015. The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice. International immunopharmacology 25: 55–64.CrossRefPubMed Chen, T., Y. Mou, J. Tan, L. Wei, Y. Qiao, T. Wei, et al. 2015. The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice. International immunopharmacology 25: 55–64.CrossRefPubMed
20.
Zurück zum Zitat Ma, C., Z. Ma, Q. Fu, and S. Ma. 2013. Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice. Fitoterapia 87: 57–64.CrossRefPubMed Ma, C., Z. Ma, Q. Fu, and S. Ma. 2013. Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice. Fitoterapia 87: 57–64.CrossRefPubMed
21.
Zurück zum Zitat Ma, C., Z. Ma, X.L. Liao, J. Liu, Q. Fu, and S. Ma. 2013. Immunoregulatory effects of glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4(+)CD25(+)Foxp3+ regulatory T cells in ovalbumin-sensitized mice. Journal of ethnopharmacology 148: 755–62.CrossRefPubMed Ma, C., Z. Ma, X.L. Liao, J. Liu, Q. Fu, and S. Ma. 2013. Immunoregulatory effects of glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4(+)CD25(+)Foxp3+ regulatory T cells in ovalbumin-sensitized mice. Journal of ethnopharmacology 148: 755–62.CrossRefPubMed
22.
Zurück zum Zitat Jiang W, Luo F, Lu Q, Liu J, Li P, Wang X, et al. 2016. The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state. Chemico-biological interactions 243: 127–34. Jiang W, Luo F, Lu Q, Liu J, Li P, Wang X, et al. 2016. The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state. Chemico-biological interactions 243: 127–34.
23.
Zurück zum Zitat Song, X., S. Xie, K. Lu, and C. Wang. 2015. Mesenchymal stem cells alleviate experimental asthma by inducing polarization of alveolar macrophages. Inflammation 38: 485–92.CrossRefPubMed Song, X., S. Xie, K. Lu, and C. Wang. 2015. Mesenchymal stem cells alleviate experimental asthma by inducing polarization of alveolar macrophages. Inflammation 38: 485–92.CrossRefPubMed
24.
Zurück zum Zitat Kang, K.S., W. Lee, Y. Jung, J.H. Lee, S. Lee, D.W. Eom, et al. 2014. Protective effect of esculin on streptozotocin-induced diabetic renal damage in mice. Journal of agricultural and food chemistry 62: 2069–76.CrossRefPubMed Kang, K.S., W. Lee, Y. Jung, J.H. Lee, S. Lee, D.W. Eom, et al. 2014. Protective effect of esculin on streptozotocin-induced diabetic renal damage in mice. Journal of agricultural and food chemistry 62: 2069–76.CrossRefPubMed
25.
Zurück zum Zitat Jang, T.Y., C.S. Park, K.S. Kim, M.J. Heo, and Y.H. Kim. 2014. Benzaldehyde suppresses murine allergic asthma and rhinitis. International immunopharmacology 22: 444–50.CrossRefPubMed Jang, T.Y., C.S. Park, K.S. Kim, M.J. Heo, and Y.H. Kim. 2014. Benzaldehyde suppresses murine allergic asthma and rhinitis. International immunopharmacology 22: 444–50.CrossRefPubMed
26.
Zurück zum Zitat Ma, C., Z. Ma, Q. Fu, and S. Ma. 2014. Anti‐asthmatic effects of baicalin in a mouse model of allergic asthma. Phytotherapy Research 28: 231–237.CrossRefPubMed Ma, C., Z. Ma, Q. Fu, and S. Ma. 2014. Anti‐asthmatic effects of baicalin in a mouse model of allergic asthma. Phytotherapy Research 28: 231–237.CrossRefPubMed
27.
Zurück zum Zitat Jiang Q, Yi M, Guo Q, Wang C, Wang H, Meng S, et al. 2015. Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-kappaB pathway. International immunopharmacology 29: 370–6. Jiang Q, Yi M, Guo Q, Wang C, Wang H, Meng S, et al. 2015. Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-kappaB pathway. International immunopharmacology 29: 370–6.
28.
Zurück zum Zitat Vroman, H., B. van den Blink, and M. Kool. 2015. Mode of dendritic cell activation: the decisive hand in Th2/Th17 cell differentiation. Implications in asthma severity? Immunobiology 220: 254–61.CrossRefPubMed Vroman, H., B. van den Blink, and M. Kool. 2015. Mode of dendritic cell activation: the decisive hand in Th2/Th17 cell differentiation. Implications in asthma severity? Immunobiology 220: 254–61.CrossRefPubMed
29.
Zurück zum Zitat Ji, N.F., Y.C. Xie, M.S. Zhang, X. Zhao, H. Cheng, H. Wang, et al. 2014. Ligustrazine corrects Th1/Th2 and Treg/Th17 imbalance in a mouse asthma model. International immunopharmacology 21: 76–81.CrossRefPubMed Ji, N.F., Y.C. Xie, M.S. Zhang, X. Zhao, H. Cheng, H. Wang, et al. 2014. Ligustrazine corrects Th1/Th2 and Treg/Th17 imbalance in a mouse asthma model. International immunopharmacology 21: 76–81.CrossRefPubMed
30.
Zurück zum Zitat Yang, X., Y. Li, Y. He, T. Li, W. Wang, J. Zhang, et al. 2015. Cordycepin alleviates airway hyperreactivity in a murine model of asthma by attenuating the inflammatory process. International immunopharmacology 26: 401–8.CrossRefPubMed Yang, X., Y. Li, Y. He, T. Li, W. Wang, J. Zhang, et al. 2015. Cordycepin alleviates airway hyperreactivity in a murine model of asthma by attenuating the inflammatory process. International immunopharmacology 26: 401–8.CrossRefPubMed
31.
Zurück zum Zitat Chung, M.J., R.P. Pandey, J.W. Choi, J.K. Sohng, D.J. Choi, and Y.I. Park. 2015. Inhibitory effects of kaempferol-3-O-rhamnoside on ovalbumin-induced lung inflammation in a mouse model of allergic asthma. International immunopharmacology 25: 302–10.CrossRefPubMed Chung, M.J., R.P. Pandey, J.W. Choi, J.K. Sohng, D.J. Choi, and Y.I. Park. 2015. Inhibitory effects of kaempferol-3-O-rhamnoside on ovalbumin-induced lung inflammation in a mouse model of allergic asthma. International immunopharmacology 25: 302–10.CrossRefPubMed
32.
Zurück zum Zitat Shin, I.S., M.Y. Lee, E.S. Cho, E.Y. Choi, H.Y. Son, and K.Y. Lee. 2014. Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma. Toxicology and applied pharmacology 274: 402–7.CrossRefPubMed Shin, I.S., M.Y. Lee, E.S. Cho, E.Y. Choi, H.Y. Son, and K.Y. Lee. 2014. Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma. Toxicology and applied pharmacology 274: 402–7.CrossRefPubMed
33.
Zurück zum Zitat Zhang T, Yang Z, Yang S, Du J, Wang S. 2015. Immunoregulatory effects of paeoniflorin exerts anti-asthmatic effects via modulation of the Th1/Th2 equilibrium. Inflammation 38: 2017–25. Zhang T, Yang Z, Yang S, Du J, Wang S. 2015. Immunoregulatory effects of paeoniflorin exerts anti-asthmatic effects via modulation of the Th1/Th2 equilibrium. Inflammation 38: 2017–25.
34.
Zurück zum Zitat Chen, T., L. Xiao, L. Zhu, S. Ma, T. Yan, and H. Ji. 2015. Anti-asthmatic effects of ginsenoside Rb1 in a mouse model of allergic asthma through relegating Th1/Th2. Inflammation 38: 1814–22.CrossRefPubMed Chen, T., L. Xiao, L. Zhu, S. Ma, T. Yan, and H. Ji. 2015. Anti-asthmatic effects of ginsenoside Rb1 in a mouse model of allergic asthma through relegating Th1/Th2. Inflammation 38: 1814–22.CrossRefPubMed
35.
Zurück zum Zitat Duan MC, Han W, Jin PW, Wei YP, Wei Q, Zhang LM, et al. 2015. Disturbed Th17/Treg balance in patients with non-small cell lung cancer. Inflammation 38: 2156–65. Duan MC, Han W, Jin PW, Wei YP, Wei Q, Zhang LM, et al. 2015. Disturbed Th17/Treg balance in patients with non-small cell lung cancer. Inflammation 38: 2156–65.
36.
Zurück zum Zitat Wang, J., L. Kong, Q. Luo, B. Li, J. Wu, B. Liu, et al. 2014. Dual effects of respiratory syncytial virus infections on airway inflammation by regulation of Th17/Treg responses in ovalbumin-challenged mice. Inflammation 37: 1984–2005.CrossRefPubMed Wang, J., L. Kong, Q. Luo, B. Li, J. Wu, B. Liu, et al. 2014. Dual effects of respiratory syncytial virus infections on airway inflammation by regulation of Th17/Treg responses in ovalbumin-challenged mice. Inflammation 37: 1984–2005.CrossRefPubMed
Metadaten
Titel
Esculetin Attenuates Th2 and Th17 Responses in an Ovalbumin-Induced Asthmatic Mouse Model
verfasst von
Long Hongyan
Publikationsdatum
21.01.2016
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 2/2016
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-015-0300-4

Weitere Artikel der Ausgabe 2/2016

Inflammation 2/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.