Regulation of Proinflammatory Mediators via NF-κB and p38 MAPK-Dependent Mechanisms in RAW 264.7 Macrophages by Polyphenol Components Isolated from Korea Lonicera japonica THUNB

Lonicera japonica THUNB., which abundantly contains polyphenols, has been used as a traditional medicine for thousands of years in East Asian countries because of the anti-inflammation properties. This study aimed to investigate the anti-inflammatory mechanism of polyphenol components isolated from Korea L. japonica T. by nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathway. Polyphenols significantly decreased lipopolysaccharide- (LPS-) induced mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as mRNA expression of tumor necrosis factor-alpha, interleukin- (IL-) 1β, and IL-6. Moreover, polyphenols inhibited nuclear translocation of NF-κB p65, phosphorylation/degradation of the inhibitor of κB, and phosphorylation of p38 MAPK, whereas the extracellular signal-regulated kinase and Janus N-terminal kinase were not affected. These results indicate that polyphenol components isolated from Korea L. japonica T. should have anti-inflammatory effect on LPS-stimulated RAW 264.7 cells through the decrease of proinflammatory mediators expression by suppressing NF-κB and p38 MAPK activity.

[1]  G L Johnson,et al.  Organization and regulation of mitogen-activated protein kinase signaling pathways. , 1999, Current opinion in cell biology.

[2]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[3]  Jun Chen,et al.  Rapid and simple method for screening of natural antioxidants from Chinese herb Flos Lonicerae Japonicae by DPPH-HPLC-DAD-TOF/MS. , 2008, Journal of separation science.

[4]  Jang-Gi Choi,et al.  Luteolin Isolated from the Flowers of Lonicera japonica Suppresses Inflammatory Mediator Release by Blocking NF-κB and MAPKs Activation Pathways in HMC-1 Cells , 2010, Molecules.

[5]  K. Knudtson,et al.  The p38 Mitogen-activated Protein Kinase Is Required for NF-κB-dependent Gene Expression , 1999, The Journal of Biological Chemistry.

[6]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[7]  K. Knudtson,et al.  The p38 mitogen-activated protein kinase is required for NF-kappaB-dependent gene expression. The role of TATA-binding protein (TBP). , 1999, The Journal of biological chemistry.

[8]  D. Thuerauf,et al.  p38 MAPK and NF-kappa B collaborate to induce interleukin-6 gene expression and release. Evidence for a cytoprotective autocrine signaling pathway in a cardiac myocyte model system. , 2000, The Journal of biological chemistry.

[9]  M. Karin,et al.  Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. , 2000, Annual review of immunology.

[10]  Sankar Ghosh,et al.  Inhibition of nuclear factor kappa B (NF-B): an emerging theme in anti-inflammatory therapies. , 2002, Molecular interventions.

[11]  W. Ko,et al.  Anti-inflammatory effect of the aqueous extract from Lonicera japonica flower is related to inhibition of NF-kappaB activation through reducing I-kappaBalpha degradation in rat liver. , 2001, International journal of molecular medicine.

[12]  J. Ashwell.  The many paths to p38 mitogen-activated protein kinase activation in the immune system , 2006, Nature Reviews Immunology.

[13]  K. Miyazawa,et al.  Regulation of Interleukin-1β-induced Interleukin-6 Gene Expression in Human Fibroblast-like Synoviocytes by p38 Mitogen-activated Protein Kinase* , 1998, The Journal of Biological Chemistry.

[14]  Hyung Gyun Kim,et al.  Inhibitory effect of 3-caffeoyl-4-dicaffeoylquinic acid from Salicornia herbacea against phorbol ester-induced cyclooxygenase-2 expression in macrophages. , 2010, Chemico-biological interactions.

[15]  P. Tak,et al.  NF-κB: a key role in inflammatory diseases , 2001 .

[16]  S. Yoshida,et al.  The role of p38 mitogen‐activated protein kinase in IL‐6 and IL‐8 production from the TNF‐α‐ or IL‐1β‐stimulated rheumatoid synovial fibroblasts , 2000 .

[17]  Hyoung‐Chun Kim,et al.  The neuroprotective effects of Lonicera japonica THUNB. against hydrogen peroxide-induced apoptosis via phosphorylation of MAPKs and PI3K/Akt in SH-SY5Y cells. , 2011, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[18]  S. Hart,et al.  Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. , 1992, The Journal of biological chemistry.

[19]  H. W. Chang,et al.  Inactivation of phospholipase A2 by naturally occurring biflavonoid, ochnaflavone. , 1994, Biochemical and biophysical research communications.

[20]  W. Marsden.  I and J , 2012 .

[21]  K. Park,et al.  Suppressive Effect on Lipopolysaccharide-Induced Proinflammatory Mediators by Citrus aurantium L. in Macrophage RAW 264.7 Cells via NF-κB Signal Pathway , 2010, Evidence-based complementary and alternative medicine : eCAM.

[22]  Ji-Yeon Kim,et al.  Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-kappaB inactivation in RAW 264.7 macrophage cells. , 2007, Biological & pharmaceutical bulletin.

[23]  Philip R. Cohen,et al.  SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin‐1 , 1995, FEBS letters.

[24]  Lei Zhao,et al.  Anti-inflammatory effects of ethyl acetate fraction from Melilotus suaveolens Ledeb on LPS-stimulated RAW 264.7 cells. , 2009, Journal of ethnopharmacology.

[25]  L. Watkins,et al.  Toll‐like receptor 4 in CNS pathologies , 2010, Journal of neurochemistry.

[26]  Hyung Keun Kim,et al.  Down-regulation of iNOS and TNF-α expression by kaempferol via NF-κB inactivation in aged rat gingival tissues , 2007, Biogerontology.

[27]  M J May,et al.  NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. , 1998, Annual review of immunology.

[28]  B. K. English,et al.  Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. , 1999, The Journal of infectious diseases.

[29]  Jerry L. Adams,et al.  A protein kinase involved in the regulation of inflammatory cytokine biosynthesis , 1994, Nature.

[30]  A. Morita,et al.  Regulation of NF‐κB Signaling by Decoy Oligodeoxynucleotides , 2006 .

[31]  H. Bartsch,et al.  Nuclear Factor κB Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms* , 2001, The Journal of Biological Chemistry.

[32]  A. Rees,et al.  Macrophage Activation and Programming and Its Role for Macrophage Function in Glomerular Inflammation , 1999, Kidney and Blood Pressure Research.

[33]  T. Moon,et al.  The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells. , 2006, Archives of biochemistry and biophysics.

[34]  M. Elder.  The Role of Cytokines , 1997 .

[35]  I. Lundberg.  The role of cytokines, chemokines, and adhesion molecules in the pathogenesis of idiopathic inflammatory myopathies , 2000, Current rheumatology reports.

[36]  K. Bae,et al.  Anti-inflammatory effect of Lonicera japonica in proteinase-activated receptor 2-mediated paw edema. , 2003, Clinica chimica acta; international journal of clinical chemistry.

[37]  Michael Kracht,et al.  Transcriptional and post-transcriptional control of gene expression in inflammation. , 2002, Cytokine.