Surfactant protein A activates NF-κB in the THP-1 monocytic cell line

Michael Koptides, Todd M. Umstead, Joanna Floros, David S. Phelps

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

The expression of many genes for which products are involved in inflammation is controlled by the transcriptional regulator nuclear factor (NF)-κB. Because surfactant protein (SP) A is involved in local host defense in the lung and alters immune cell function by modulating the expression of proinflammatory cytokines as well as surface proteins involved in inflammation, we hypothesized that SP-A exerts its action, at least in part, via activation of NF-κB. We used gel shift assays to determine whether SP-A activated NF-κB in the THP-1 cell line, a human monocytic cell line. Activation of NF-κB in THP-1 cells by SP-A doses as low as 1 μg/ml occurred within 30 min of SPA treatment, peaked at 60 min, and then declined. This activation is inhibited by known inhibitors of NF-κB or by simultaneous treatment of the cells with surfactant lipids. Moreover, the NF-κB inhibitors blocked SP-A-dependent increases in tumor necrosis factor-α mRNA levels. These observations suggest a mechanism by which SP-A plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent SP-A induced inflammation in the lung.

Original languageEnglish (US)
Pages (from-to)L382-L388
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume273
Issue number2 17-2
DOIs
StatePublished - 1997

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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