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

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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume273
Issue number2 17-2
StatePublished - Oct 18 1997

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Pulmonary Surfactant-Associated Protein A
Cell Line
Inflammation
Lung
Surface-Active Agents
Pneumonia
Membrane Proteins
Tumor Necrosis Factor-alpha
Gels
Cytokines
Lipids
Gene Expression
Messenger RNA

All Science Journal Classification (ASJC) codes

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

Cite this

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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.",
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Surfactant protein A activates NF-κB in the THP-1 monocytic cell line. / Koptides, Michael; Umstead, Todd M.; Floros, Joanna; Phelps, David.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 273, No. 2 17-2, 18.10.1997.

Research output: Contribution to journalArticle

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AU - Umstead, Todd M.

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