Suppression of endotoxin-induced proinflammatory responses by citrus pectin through blocking LPS signaling pathways.

Abstract

Pectin is composed of complex polysaccharides rich in galactoside residues, and it is most abundant in citrus fruits. Pectin and modified pectin have been found to exhibit anti-mutagenic activity and inhibit cancer metastasis and proliferation, with no evidence of toxicity or other serious side effects. In this study, we investigated the inhibitory effect of pectin at different degrees of esterification (DEs) on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-activated macrophages. Western blot and RT-PCR analyses demonstrated that 30% esterified pectin (DE30), DE60 pectin, and DE90 pectin significantly inhibited the protein and mRNA expressions of iNOS and COX-2 in LPS-activated macrophages, and DE90 pectin was the most-potent inhibitor. To clarify the mechanisms involved, DE90 pectin was found to inhibit the phosphorylation of MAPKs and IKK kinase activity. In addition, DE90 pectin inhibited the activation of NF-kappaB and AP-1 by electrophoretic mobility shift assay and transient transfection experiments. Finally, we found that DE90 pectin could bind with LPS, and might result in decreased binding of LPS to its receptor. These results suggest that modulation of iNOS and COX-2 expressions by dietary pectin may be important in cancer chemoprevention and anti-inflammation.

• Authors: Chien-Ho Chen, Ming-Thau Sheu, Tzeng-Fu Chen, Ying-Ching Wang, Wen-Chi Hou, Der-Zen Liu, Tsao-Chuen Chung, Yu-Chih Liang
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 72 Issue 8 Pg. 1001-9 (Oct 16 2006) ISSN: 0006-2952 [Print] England
• PMID: 16930561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclooxygenase 2 Inhibitors
• I-kappa B Proteins
• Lipopolysaccharides
• NF-kappa B
• Nfkbia protein, mouse
• RNA, Messenger
• Transcription Factor AP-1
• NF-KappaB Inhibitor alpha
• Pectins
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Cyclooxygenase 2
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Cell Line
• Cell Survival (drug effects)
• Citrus
• Cyclooxygenase 2 (genetics, metabolism)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects)
• I-kappa B Proteins (metabolism)
• Inflammation (chemically induced, prevention & control)
• Lipopolysaccharides (pharmacology)
• Macrophages, Peritoneal (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinases (metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (antagonists & inhibitors, genetics, metabolism)
• Pectins (pharmacology)
• Promoter Regions, Genetic (drug effects)
• RNA, Messenger (metabolism)
• Signal Transduction (drug effects)
• Transcription Factor AP-1 (metabolism)