Lipopolysaccharide induces CXCL2/macrophage inflammatory protein-2 gene expression in enterocytes via NF-κB activation: Independence from endogenous TNF-α and platelet-activating factor

Isabelle G. De Plaen*, Xin Bing Han, Xueli Liu, Wei Hsueh, Sankar Ghosh, Michael J. May

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

CXCL2 (macrophage inflammatory protein-2 (MIP-2)), a critical chemokine for neutrophils, has been shown to be produced in the rat intestine in response to platelet-activating factor (PAF) and to mediate intestinal inflammation and injury. The intestinal epithelium, constantly exposed to bacterial products, is the first line of defence against micro-organisms. It has been reported that enterocytes produce proinflammatory mediators, including tumour necrosis factor (TNF) and PAF, and we showed that lipopolysaccharide (LPS) and TNF activate nuclear factor (NF)-κB in enterocytes. However, it remains elusive whether enterocytes release CXCL2 in response to LPS and TNF via a NF-κB- dependent pathway and whether this involves the endogenous production of TNF and PAF. In this study, we found that TNF and LPS markedly induced CXCL2 gene expression in IEC-6 cells, TNF within 30 min, peaking at 45 min, while LPS more slowly, peaking after 2 hr. TNF- and LPS- induced CXCL2 gene expression and protein release were completely blocked by pyrrolidine dithiocarbamate (PDTC) and helenalin, two potent NF-κB inhibitors. NEMO-binding domain peptide, a specific inhibitor of inhibitor protein κB kinase (IKK) activation, a major upstream kinase mediating NF-κB activation, significantly blocked CXCL2 gene expression and protein release induced by LPS. WEB2170 (PAF antagonist) and anti-TNF antibodies had no effect on LPS-induced CXCL2 expression. In conclusion, CXCL2 gene is expressed in enterocytes in response to both TNF and LPS. LPS-induced CXCL2 expression is dependent on NF-κB activation via the IKK pathway. The effect of LPS is independent of endogenous TNF and PAF.

Original languageEnglish (US)
Pages (from-to)153-163
Number of pages11
JournalImmunology
Volume118
Issue number2
DOIs
StatePublished - Jun 2006

Keywords

  • CXCL2 (MIP-2)
  • Chemokine
  • Intestine
  • LPS
  • Nuclear factor-κB
  • TNF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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