Induction of proinflammatory mediators requires activation of the TRAF, NIK, IKK and NF‐κB signal transduction pathway in astrocytes infected with Escherichia coli

Abstract

Escherichia coli is associated with inflammation in the brain. To investigate whether astrocytes are involved in E. coli-induced inflammation, we assessed the levels of expression of proinflammatory mediators produced by E. coli-infected astrocytes. E. coli infection in primary human astrocytes and cell lines increased expression of the CXC chemokine IL-8/GRO-alpha, the CC chemokine MCP-1, TNF-alpha, and iNOS. E. coli infection activated p65/p50 heterodimeric NF-kappa B and concurrently decreased the signals of I kappa B alpha. Blocking the NF-kappa B signals by I kappa B alpha-superrepressor-containing retrovirus or antisense p50 oligonucleotide transfection resulted in down-regulation of expression of the proinflammatory mediators. Furthermore, superrepressors of I kappa B alpha, I kappa B kinase (IKK) or NF-kappa B inducing kinase (NIK) inhibited the up-regulated expression of the downstream target genes of NF-kappa B such as IL-8 and MCP-1, and superrepressors of TNF receptor-associated factor (TRAF)2 and TRAF5 also inhibited expression of the E. coli-induced target genes of NF-kappa B. These results indicate that proinflammatory mediators such as the CXC chemokine IL-8/GRO-alpha, the CC chemokine MCP-1, TNF-alpha, and iNOS can be expressed in E. coli-infected astrocytes via an NF-kappa B pathway, suggesting that these mediators may contribute to inflammation in the brain, including infiltration of inflammatory cells.