Inhibitory effect of ZPDC glycoprotein on the expression of inflammation-related cytokines through p38 MAP kinase and JNK in lipopolysaccharide-stimulated RAW 264.7 cells

• Published in: Inflammation research Vol. 58; no. 4; pp. 184 - 191
• Main Authors: Lee, S.-J., Lim, K.-T.
• Format: Journal Article
• Language: English
• Published: Basel Birkhäuser-Verlag 01-04-2009; Springer Nature B.V
• Subjects: Allergology; Animals; Antioxidants - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Line; Cytokines - immunology; Dermatology; Enzyme Inhibitors - metabolism; Glycoproteins - metabolism; Immunology; Inflammation - immunology; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; Macrophages - cytology; Macrophages - drug effects; Macrophages - immunology; Mice; Neurology; Nitric Oxide - metabolism; Oxidants - metabolism; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pharmacology/Toxicology; Rheumatology; Second Messenger Systems - physiology; Zanthoxylum; Zanthoxylum - chemistry; c-Jun N-terminal kinase; Pro-inflammatory mediators; ZPDC glycoprotein; Anti-inflammatory potentials; RAW 264.7 cells
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-008-8118-2

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Objective:
This study was carried out to investigate the anti-inflammatory potentials of 24 kDa glycoprotein isolated from
Zanthoxylum piperitum
DC fruit (ZPDC glycoprotein) in lipopolysaccharide (LPS)-stimulated murine macrophage cell line (RAW 264.7 cells).
Material and Methods:
RAW 264.7 cells were treated with ZPDC glycoprotein (50–200 μg/ml) in presence of LPS (2 μg/ml). The changes of the levels of inflammation-related factors were determined by using Western blot, EMSA, and RT-PCR.
Results:
ZPDC glycoprotein has inhibitory effects on the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK), on the DNA binding activity of activator protein-1 (AP-1), and on the expression of c-Jun and c-Fos in LPS-stimulated RAW 264.7 cells. Interestingly, the DNA binding activity of AP-1 was attenuated by treatment with inhibitors of p38 MAP kinase and JNK. In addition, ZPDC glycoprotein (200 μg/ml) not only diminished the production of superoxide anion, hydrogen peroxide, and nitric oxide, but also suppressed the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and proteins (iNOS, COX-2, and MMP-9) in LPS- stimulated RAW 264.7 cells.
Conclusions:
The present study demonstrates that ZPDC glycoprotein is a natural anti-oxidant and one of the modulators of pro-inflammatory signal transduction pathways in RAW 264.7 cells.