Skip to main content

Advertisement

SpringerLink
Log in

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

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Page, R.C. 1991. The role of inflammatory mediators in the pathogenesis of periodontal disease. Journal of Periodontal Research 26: 230–242.

    Article  CAS  PubMed  Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hienz, S.A., S. Paliwal, and S. Ivanovski. 2015. Mechanisms of bone resorption in periodontitis. Journal of Immunology Research 2015: 615486.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. 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. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by JSPS KAKENHI (Grant Numbers: 16K11834 and 18K09600).

Author information

Authors and Affiliations

  1. Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8504, Japan

    Ikuko Hosokawa, Yoshitaka Hosokawa & Takashi Matsuo

  2. Department of Oral Health Care Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima, Japan

    Kazumi Ozaki

Authors
  1. Ikuko Hosokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshitaka Hosokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazumi Ozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Matsuo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshitaka Hosokawa.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hosokawa, I., Hosokawa, Y., Ozaki, K. et al. Carnosic Acid Inhibits CXCR3 Ligands Production in IL-27-Stimulated Human Oral Epithelial Cells. Inflammation 42, 1311–1316 (2019). https://doi.org/10.1007/s10753-019-00991-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-019-00991-6

KEY WORDS

Search

Navigation