Abstract
This report describes the anti-inflammatory effects of MeOH extract from leaves of Carpinus tschonoskii (CE) on primary bone marrow-derived macrophage (BMDMs) and dendritic cells (BMDCs). Primary BMDMs and BMDCs were used for pro-inflammatory cytokine production and Western blot analysis. Human embryonic kidney cell line 293 T (HEK293 T) was used to access NF-κB activity. In all cases, CpG DNA was used to stimulate the cells. The CE (0–150 μg/ml) was treated to BMDMs, BMDCs, and HEK293T cells. CE pre-treatment in CpG-stimulated BMDMs and BMDCs showed a dose-dependent inhibitory effect on pro-inflammatory cytokine (e.g., IL-12 p40, IL-6, and TNF-α) production as compared to non-treated controls. The CE pre-treatment had no significant inhibition on mitogen-activated protein kinases (MAPKs) phosphorylation but strongly inhibited IκBα degradation. In NF-κB reporter gene assay, the CE pre-treatment inhibited NF-κB-dependent luciferase activity in a dose-dependent manner. Taken together, these data suggest that CE has significant inhibitory effect on pro-inflammatory cytokine production and warrant further studies concerning potentials of CE for medicinal uses.
Similar content being viewed by others
References
Akira S.; Takeda K.; Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2: 675–680; 2001.
Bao L.; Lindgren J. U.; van der Meide P.; Zhu S.; Ljunggren H. G.; Zhu J. The critical role of IL-12 p40 in initiating, enhancing, and perpetuating pathogenic events in murine experimental autoimmune neuritis. Brain Pathol. 12: 420–429; 2002.
Bollrath J.; Phesse T. J.; von Burstin V. A.; Putoczki T.; Bennecke M.; Bateman T.; Nebelsiek T.; Lundgren-May T.; Canli O.; Schwitalla S.; Matthews V.; Schmid R. M.; Kirchner T.; Arkan M. C.; Ernst M.; Greten F. R. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15: 91–102; 2009.
Bromberg J.; Wang T. C. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 15: 79–80; 2009.
Chang C. S.; Chang K. S. Typification of Corylopsis coreana (Hamamelidaceae) and Carpinus laxiflora var. longispica (Betulaceae). J. Jpn. Bot. 85: 270–276; 2010.
Efron P. A.; Tsujimoto H.; Bahjat F. R.; Ungaro R.; Debernardis J.; Tannahill C.; Baker H. V.; Edwards C. K.; Moldawer L. L. Differential maturation of murine bone-marrow derived dendritic cells with lipopolysaccharide and tumor necrosis factor-α. J. Endotoxin Res. 11: 145–160; 2005.
Feldmann M.; Maini R. N. Anti-TNF α therapy of rheumatoid arthritis: what have we learned? Annu. Rev. Immunol. 19: 163–196; 2001.
Gilliet M.; Cao W.; Liu Y. J. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat. Rev. Immunol. 8: 594–606; 2008.
Grivennikov S.; Karin E.; Terzic J.; Mucida D.; Yu G. Y.; Vallabhapurapu S.; Scheller J.; Rose-John S.; Cheroutre H.; Eckmann L.; Karin M. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15: 103–113; 2009.
Heinrich P. C.; Behrmann I.; Muller-Newen G.; Schaper F.; Graeve L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem. J. 334: 297–314; 1998.
Ishii K. J.; Koyama S.; Nakagawa A.; Coban C.; Akira S. Host innate immune receptors and beyond: making sense of microbial infections. Cell Host Microbe. 3: 352–363; 2008.
Kawai T.; Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11: 373–384; 2010.
Koh Y. S. Nucleic acid recognition and signaling by Toll-like receptor 9: compartment-dependent regulation. J. Bacteriol. Virol. 41: 131–132; 2011.
Lampropoulou V.; Hoehlig K.; Roch T.; Neves P.; Calderón G. E.; Sweenie C. H.; Hao Y.; Freitas A. A.; Steinhoff U.; Anderton S. M.; Fillatreau S. TLR-activated B cells suppress T cell-mediated autoimmunity. J. Immunol. 180: 4763–4773; 2008.
Medzhitov R. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1: 135–145; 2001.
Opal S. M.; DePalo V. A. Anti-inflammatory cytokines. Chest 117: 1162–1172; 2000.
Roux P. P.; Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68: 320–344; 2004.
Takeuchi O.; Akira S. Pattern recognition receptors and inflammation. Cell 140: 805–820; 2010.
Trikha M.; Corringham R.; Klein B.; Rossi J. F. Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin. Cancer Res. 9: 4653–4665; 2003.
Yasuda K.; Richez C.; Uccellini M. B.; Richards R. J.; Bonegio R. G.; Akira S.; Monestier M.; Corley R. B.; Viglianti G. A.; Marshak-Rothstein A.; Rifkin I. R. Requirement for DNA CpG content in TLR9-dependent dendritic cell activation induced by DNA-containing immune complexes. J. Immunol. 183: 3109–3117; 2009.
Yuk J. M.; Jo E. K. Toll-like receptors and innate immunity. J. Bacteriol. Virol. 41: 225–235; 2011.
Yun J. H.; Koo J. E.; Koh Y. S. Mitogen-activated protein kinases and tumor necrosis factor alpha responses of macrophages infected with Orientia tsutsugamushi. World J. Microbiol. Biotechnol. 25: 2157–2164; 2009.
Zhang R.; Kang K. A.; Piao M. J.; Park J. W.; Shin T.; Yoo B. S.; Yang Y. T.; Hyun J. W. Cytoprotective activity of Carpinus tschonoskii against H2O2 induced oxidative stress. Nat. Prod. Sci. 13: 118–122; 2007.
Acknowledgment
This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1120340).
Conflict of interest
The authors declare that there are no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Koo, JE., Hong, HJ., Mathema, V.B. et al. Inhibitory effects of Carpinus tschonoskii leaves extract on CpG-stimulated pro-inflammatory cytokine production in murine bone marrow-derived macrophages and dendritic cells. In Vitro Cell.Dev.Biol.-Animal 48, 197–202 (2012). https://doi.org/10.1007/s11626-012-9495-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11626-012-9495-y