Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase expression by endoplasmic reticulum stress

Hui Ju Ho, Duen Yi Huang, Feng Ming Ho, Long Teng Lee, Wan Wan Lin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Endoplasmic reticulum (ER) stress is induced in infectious and inflammatory conditions, but its role in inflammatory responses still remains elusive. In this study we found tunicamycin (TM) and brefeldin A (BFA), two ER stressors, could attenuate lipopolysaccharide (LPS)-elicited inducible nitric oxide synthase (iNOS) gene expression in murine RAW264.7 macrophages, and this effect was not resulting from the effects on IKK or MAPKs activation. However, ER stressors could block NF-κB binding to the iNOS promoter in late-phase signaling evoked by LPS. Results indicated that inhibition of RelB nuclear translocation and p300 expression are involved in the anti-inflammatory actions of ER stressors. We also found that ER stressors could block LPS- and IFN (α, β, and γ)-mediated STAT1 phosphorylation. Our results suggest that activation of MKP-1 via a Ca/calmodulin/calcineurin pathway accounts for the inhibitory effect of ER stressors on IFN signaling. MKP-1 was downregulated by IFN-γ and is a newly identified protein phosphatase targeting STAT1. Taken together, these results indicate that multiple mechanisms are involved in the inhibition of LPS-induced iNOS gene expression by ER stressors. These include downregulation of RelB and p300, upregulation of MKP-1, and inhibition of the JAK/STAT signaling pathway.

Original languageEnglish
Pages (from-to)2166-2178
Number of pages13
JournalCellular Signalling
Volume24
Issue number11
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Endoplasmic Reticulum Stress
Nitric Oxide Synthase Type II
Endoplasmic Reticulum
Lipopolysaccharides
Down-Regulation
Brefeldin A
Gene Expression
Tunicamycin
Calcineurin
Phosphoprotein Phosphatases
Protein Transport
Calmodulin
Anti-Inflammatory Agents
Up-Regulation
Macrophages
Phosphorylation

Keywords

  • ER stress
  • LPS
  • NF-κB
  • PTP
  • STAT

ASJC Scopus subject areas

  • Cell Biology

Cite this

Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase expression by endoplasmic reticulum stress. / Ho, Hui Ju; Huang, Duen Yi; Ho, Feng Ming; Lee, Long Teng; Lin, Wan Wan.

In: Cellular Signalling, Vol. 24, No. 11, 11.2012, p. 2166-2178.

Research output: Contribution to journalArticle

Ho, Hui Ju ; Huang, Duen Yi ; Ho, Feng Ming ; Lee, Long Teng ; Lin, Wan Wan. / Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase expression by endoplasmic reticulum stress. In: Cellular Signalling. 2012 ; Vol. 24, No. 11. pp. 2166-2178.
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