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Published in: Inflammation 4/2019

01-08-2019 | Gingival Diseases | ORIGINAL ARTICLE

Carnosic Acid Inhibits CXCR3 Ligands Production in IL-27-Stimulated Human Oral Epithelial Cells

Authors: Ikuko Hosokawa, Yoshitaka Hosokawa, Kazumi Ozaki, Takashi Matsuo

Published in: Inflammation | Issue 4/2019

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Abstract

Carnosic acid, which is a bioactive compound isolated from rosemary, has various pharmacological effects. However, the anti-inflammatory effect of carnosic acid on periodontitis is still unknown. The aim of this study was to investigate the effect of carnosic acid on CXC chemokine receptor 3 (CXCR3) ligands, which are involved in Th1 cells migration and accumulation, production in interleukin (IL)-27-stimulated human oral epithelial cells (TR146 cells). Carnosic acid decreased CXC chemokine ligand (CXCL)9, CXCL10, and CXCL11 production in IL-27-stimulated TR146 cells in a dose-dependent fashion. Moreover, we disclosed that carnosic acid could suppress signal transducer and activator of transcription (STAT)1, STAT3, and protein kinase B (Akt) phosphorylation in IL-27-stimulated TR146 cells. Furthermore, STAT1, STAT3, and Akt inhibitors could suppress CXCR3 ligands production in IL-27-treated TR146 cells. In summary, carnosic acid could reduce CXCR3 ligands production in human oral epithelial cell by inhibiting STAT1, STAT3, and Akt activation.
Literature
1.
go back to reference Page, R.C. 1991. The role of inflammatory mediators in the pathogenesis of periodontal disease. Journal of Periodontal Research 26: 230–242.CrossRefPubMed Page, R.C. 1991. The role of inflammatory mediators in the pathogenesis of periodontal disease. Journal of Periodontal Research 26: 230–242.CrossRefPubMed
2.
go back to reference Kawai, T., R. Eisen-Lev, M. Seki, J.W. Eastcott, M.E. Wilson, and M.A. Taubman. 2000. Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease. Journal of Immunology 64: 2102–2109.CrossRef Kawai, T., R. Eisen-Lev, M. Seki, J.W. Eastcott, M.E. Wilson, and M.A. Taubman. 2000. Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease. Journal of Immunology 64: 2102–2109.CrossRef
3.
go back to reference Zhang, X., and Y.T. Teng. 2006. Interleukin-10 inhibits gram-negative-microbe-specific human receptor activator of NF-kappaB ligand-positive CD4+-Th1-cell-associated alveolar bone loss in vivo. Infection and Immunity 74: 4927–4931.CrossRefPubMedPubMedCentral Zhang, X., and Y.T. Teng. 2006. Interleukin-10 inhibits gram-negative-microbe-specific human receptor activator of NF-kappaB ligand-positive CD4+-Th1-cell-associated alveolar bone loss in vivo. Infection and Immunity 74: 4927–4931.CrossRefPubMedPubMedCentral
5.
go back to reference Heise, C.E., A. Pahuja, S.C. Hudson, M.S. Mistry, A.L. Putnam, M.M. Gross, P.A. Gottlieb, W.S. Wade, M. Kiankarimi, D. Schwarz, P. Crowe, A. Zlotnik, and D.G. Alleva. 2005. Pharmacological characterization of CXC chemokine receptor 3 ligands and a small molecule antagonist. The Journal of Pharmacology and Experimental Therapeutics 313: 1263–1271.CrossRefPubMed Heise, C.E., A. Pahuja, S.C. Hudson, M.S. Mistry, A.L. Putnam, M.M. Gross, P.A. Gottlieb, W.S. Wade, M. Kiankarimi, D. Schwarz, P. Crowe, A. Zlotnik, and D.G. Alleva. 2005. Pharmacological characterization of CXC chemokine receptor 3 ligands and a small molecule antagonist. The Journal of Pharmacology and Experimental Therapeutics 313: 1263–1271.CrossRefPubMed
6.
go back to reference Hosokawa, Y., I. Hosokawa, K. Ozaki, and T. Matsuo. 2017. IL-27 modulates chemokine production in TNF-α -stimulated human oral epithelial cells. Cellular Physiology and Biochemistry 43: 1198–1206.CrossRefPubMed Hosokawa, Y., I. Hosokawa, K. Ozaki, and T. Matsuo. 2017. IL-27 modulates chemokine production in TNF-α -stimulated human oral epithelial cells. Cellular Physiology and Biochemistry 43: 1198–1206.CrossRefPubMed
7.
go back to reference Thummuri, D., V.G.M. Naidu, and P. Chaudhari. 2017. Carnosic acid attenuates RANKL-induced oxidative stress and osteoclastogenesis via induction of Nrf2 and suppression of NF-κB and MAPK signalling. Journal of Molecular Medicine 95: 1065–1076.CrossRefPubMed Thummuri, D., V.G.M. Naidu, and P. Chaudhari. 2017. Carnosic acid attenuates RANKL-induced oxidative stress and osteoclastogenesis via induction of Nrf2 and suppression of NF-κB and MAPK signalling. Journal of Molecular Medicine 95: 1065–1076.CrossRefPubMed
8.
go back to reference Vázquez, N.M., G. Fiorilli, P.A. Cáceres Guido, and S. Moreno. 2016. Carnosic acid acts synergistically with gentamicin in killing methicillin-resistant Staphylococcus aureus clinical isolates. Phytomedicine. 23: 1337–1343.CrossRefPubMed Vázquez, N.M., G. Fiorilli, P.A. Cáceres Guido, and S. Moreno. 2016. Carnosic acid acts synergistically with gentamicin in killing methicillin-resistant Staphylococcus aureus clinical isolates. Phytomedicine. 23: 1337–1343.CrossRefPubMed
9.
go back to reference Su, K., C.F. Wang, Y. Zhang, Y.J. Cai, Y.Y. Zhang, and Q. Zhao. 2016. The inhibitory effects of carnosic acid on cervical cancer cells growth by promoting apoptosis via ROS-regulated signaling pathway. Biomedicine & Pharmacotherapy 82: 180–191.CrossRef Su, K., C.F. Wang, Y. Zhang, Y.J. Cai, Y.Y. Zhang, and Q. Zhao. 2016. The inhibitory effects of carnosic acid on cervical cancer cells growth by promoting apoptosis via ROS-regulated signaling pathway. Biomedicine & Pharmacotherapy 82: 180–191.CrossRef
10.
go back to reference Gaya, M., V. Repetto, J. Toneatto, C. Anesini, G. Piwien-Pilipuk, and S. Moreno. 2013. Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus officinalis, is exerted through the C/EBPs and PPARγ pathways at the onset of the differentiation program. Biochimica et Biophysica Acta 1830: 3796–3806. Gaya, M., V. Repetto, J. Toneatto, C. Anesini, G. Piwien-Pilipuk, and S. Moreno. 2013. Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus officinalis, is exerted through the C/EBPs and PPARγ pathways at the onset of the differentiation program. Biochimica et Biophysica Acta 1830: 3796–3806.
11.
go back to reference Jacobsen, J., E.B. Nielsen, K. Brøndum-Nielsen, M.E. Christensen, H.B. Olin, N. Tommerup, and M.R. Rassing. 1999. Filter-grown TR146 cells as an in vitro model of human buccal epithelial permeability. European Journal of Oral Sciences 107: 138–146.CrossRefPubMed Jacobsen, J., E.B. Nielsen, K. Brøndum-Nielsen, M.E. Christensen, H.B. Olin, N. Tommerup, and M.R. Rassing. 1999. Filter-grown TR146 cells as an in vitro model of human buccal epithelial permeability. European Journal of Oral Sciences 107: 138–146.CrossRefPubMed
12.
go back to reference Garlet, G.P., W. Martins Jr., B.R. Ferreira, C.M. Milanezi, and J.S. Silva. 2003. Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease. Journal of Periodontal Research 38: 210–217.CrossRefPubMed Garlet, G.P., W. Martins Jr., B.R. Ferreira, C.M. Milanezi, and J.S. Silva. 2003. Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease. Journal of Periodontal Research 38: 210–217.CrossRefPubMed
13.
go back to reference Hosokawa, Y., I. Hosokawa, K. Ozaki, and T. Matsuo. 2018. Honokiol and magnolol inhibit CXCL10 and CXCL11 production in IL-27-stimulated human oral epithelial cells. Inflammation 41: 2110–2115.CrossRefPubMed Hosokawa, Y., I. Hosokawa, K. Ozaki, and T. Matsuo. 2018. Honokiol and magnolol inhibit CXCL10 and CXCL11 production in IL-27-stimulated human oral epithelial cells. Inflammation 41: 2110–2115.CrossRefPubMed
14.
go back to reference Hosokawa, Y., I. Hosokawa, K. Ozaki, H. Nakae, and T. Matsuo. 2009 Apr. Cytokines differentially regulate CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated human gingival fibroblasts. Journal of Periodontal Research 44 (2): 225–231.CrossRefPubMed Hosokawa, Y., I. Hosokawa, K. Ozaki, H. Nakae, and T. Matsuo. 2009 Apr. Cytokines differentially regulate CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated human gingival fibroblasts. Journal of Periodontal Research 44 (2): 225–231.CrossRefPubMed
15.
go back to reference Hosokawa, Y., I. Hosokawa, K. Ozaki, H. Nakae, and T. Matsuo. 2010. TNFSF14 coordinately enhances CXCL10 and CXCL11 productions from IFN-gamma-stimulated human gingival fibroblasts. Molecular Immunology 47: 666–670.CrossRefPubMed Hosokawa, Y., I. Hosokawa, K. Ozaki, H. Nakae, and T. Matsuo. 2010. TNFSF14 coordinately enhances CXCL10 and CXCL11 productions from IFN-gamma-stimulated human gingival fibroblasts. Molecular Immunology 47: 666–670.CrossRefPubMed
16.
go back to reference Hosokawa, Y., I. Hosokawa, K. Ozaki, T. Nakanishi, H. Nakae, and T. Matsuo. 2010 Jul. Catechins inhibit CXCL10 production from oncostatin M-stimulated human gingival fibroblasts. The Journal of Nutritional Biochemistry 21 (7): 659–664.CrossRefPubMed Hosokawa, Y., I. Hosokawa, K. Ozaki, T. Nakanishi, H. Nakae, and T. Matsuo. 2010 Jul. Catechins inhibit CXCL10 production from oncostatin M-stimulated human gingival fibroblasts. The Journal of Nutritional Biochemistry 21 (7): 659–664.CrossRefPubMed
17.
go back to reference Liu, M., X. Zhou, L. Zhou, Z. Liu, J. Yuan, J. Cheng, J. Zhao, L. Wu, H. Li, H. Qiu, and J. Xu. 2018. Carnosic acid inhibits inflammation response and joint destruction on osteoclasts, fibroblast-like synoviocytes, and collagen-induced arthritis rats. Journal of Cellular Physiology 233: 6291–6303.CrossRefPubMed Liu, M., X. Zhou, L. Zhou, Z. Liu, J. Yuan, J. Cheng, J. Zhao, L. Wu, H. Li, H. Qiu, and J. Xu. 2018. Carnosic acid inhibits inflammation response and joint destruction on osteoclasts, fibroblast-like synoviocytes, and collagen-induced arthritis rats. Journal of Cellular Physiology 233: 6291–6303.CrossRefPubMed
18.
go back to reference Kida, Y., M. Kobayashi, T. Suzuki, A. Takeshita, Y. Okamatsu, S. Hanazawa, T. Yasui, and K. Hasegawa. 2005. Interleukin-1 stimulates cytokines, prostaglandin E2 and matrix metalloproteinase-1 production via activation of MAPK/AP-1 and NF-kappaB in human gingival fibroblasts. Cytokine. 29: 159–168.CrossRefPubMed Kida, Y., M. Kobayashi, T. Suzuki, A. Takeshita, Y. Okamatsu, S. Hanazawa, T. Yasui, and K. Hasegawa. 2005. Interleukin-1 stimulates cytokines, prostaglandin E2 and matrix metalloproteinase-1 production via activation of MAPK/AP-1 and NF-kappaB in human gingival fibroblasts. Cytokine. 29: 159–168.CrossRefPubMed
19.
go back to reference Rizzo, A., N. Bevilacqua, L. Guida, M. Annunziata, C. Romano Carratelli, and R. Paolillo. 2012. Effect of resveratrol and modulation of cytokine production on human periodontal ligament cells. Cytokine. 60: 197–204.CrossRefPubMed Rizzo, A., N. Bevilacqua, L. Guida, M. Annunziata, C. Romano Carratelli, and R. Paolillo. 2012. Effect of resveratrol and modulation of cytokine production on human periodontal ligament cells. Cytokine. 60: 197–204.CrossRefPubMed
20.
go back to reference Kim, D.H., K.W. Park, I.G. Chae, J. Kundu, E.H. Kim, J.K. Kundu, and K.S. Chun. 2016. Carnosic acid inhibits STAT3 signaling and induces apoptosis through generation of ROS in human colon cancer HCT116 cells. Molecular Carcinogenesis 55: 1096–1110.CrossRefPubMed Kim, D.H., K.W. Park, I.G. Chae, J. Kundu, E.H. Kim, J.K. Kundu, and K.S. Chun. 2016. Carnosic acid inhibits STAT3 signaling and induces apoptosis through generation of ROS in human colon cancer HCT116 cells. Molecular Carcinogenesis 55: 1096–1110.CrossRefPubMed
21.
go back to reference Kar, S., S. Palit, W.B. Ball, and P.K. Das. 2012. Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis. 17: 735–747.CrossRefPubMed Kar, S., S. Palit, W.B. Ball, and P.K. Das. 2012. Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis. 17: 735–747.CrossRefPubMed
Metadata
Title
Carnosic Acid Inhibits CXCR3 Ligands Production in IL-27-Stimulated Human Oral Epithelial Cells
Authors
Ikuko Hosokawa
Yoshitaka Hosokawa
Kazumi Ozaki
Takashi Matsuo
Publication date
01-08-2019
Publisher
Springer US
Published in
Inflammation / Issue 4/2019
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-019-00991-6

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