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Inflammation

, 32:372 | Cite as

Nod2 Mutation Enhances NF-kappaB Activity and Bacterial Killing Activity of Macrophages

  • Tzyy-Bin Tsay
  • Chien-Jen Chang
  • Pei-Hsuan Chen
  • Ching-Mei Hsu
  • Lee-Wei Chen
Article

Abstract

NOD2, an intracellular sensor of bacteria, are linked to increased susceptibility to bacteria in Crohn’s disease (CD). The NOD2 protein is expressed mainly by macrophages and dendritic cells. This study is to examine the role of NOD2 in the innate response of macrophages to bacterial challenge. First, peritoneal macrophages and alveolar macrophages were harvested from WT, Nod22939iC, as well as TLR4−/− mice and incubated with E. coli or P. aeruginosa. Bacterial killing activity; IL-1β and TLR4 protein expression; NF-κB DNA binding activity assay; as well as IL-1β, TNFα, TLR2, TLR4 and TLR9 mRNA expression of macrophages were examined. We found that alveolar macrophages and peritoneal macrophages of Nod22939iC mice but not WT mice or TLR4−/− mice demonstrated a significant increase of E. coli killing activity. Bacterial challenge also induced a significant increase of pro-IL-1β protein expression; NF-κB DNA binding activity; as well as IL-1β and TNFα mRNA expression of the peritoneal macrophages in Nod22939iC mice. Collectively, the increase of bacterial killing activity, IL-1β expression, and NF-κB DNA binding activity of macrophages in Nod22939iC mice suggests that NOD2 is a positive regulator of NF-κB/IL-1β-mediated innate response to bacteria challenge in Crohn’s disease.

KEY WORDS

NOD2 IL-1β bacterial killing activity TNFα NF-κB phagocytic activity 

Notes

Acknowledgements

This work was supported by grants from National Science Council (NSC932314B075B005), Kaohsiung Veterans General Hospital (VGHNSU93-04, VGHKS93-94), National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, and VTY Joint Research Program, Tsou’s Foundation (VTY92-P3-19) to CLW. The authors have declared that no conflict of interest exists.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Tzyy-Bin Tsay
    • 1
  • Chien-Jen Chang
    • 2
  • Pei-Hsuan Chen
    • 3
  • Ching-Mei Hsu
    • 4
  • Lee-Wei Chen
    • 2
    • 3
  1. 1.Department of SurgeryZuoying Armed Forces General HospitalKaohsiungTaiwan
  2. 2.Institute of Emergency and Critical Care MedicineNational Yang-Ming UniversityTaipeiTaiwan
  3. 3.Department of SurgeryKaohsiung Veterans General HospitalKaohsiungTaiwan
  4. 4.Department of Biological SciencesNational Sun Yat-Sen UniversityKaohsiungTaiwan

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