L-Arginine attenuates lipopolysaccharide-induced lung chemokine production

Casey M. Calkins, Denis D. Bensard, Julie K. Heimbach, Xianzhong Meng, Brian D. Shames, Edward J. Pulido, Robert C. McIntyre

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Chemokines stimulate the influx of leukocytes into tissues. Their production is regulated by nuclear factor-κB (NF-κB), an inducible transcription factor under the control of inhibitory factor κB-α (IκB-α). We have previously demonstrated that L-arginine (L-Arg) attenuates neutrophil accumulation and pulmonary vascular injury after administration of lipopolysaccharide (LPS). We hypothesized that L-Arg would attenuate the production of lung chemokines by stabilizing IκB-α and preventing NF-κB DNA binding. We examined the effect of L-Arg on chemokine production, IκB-α degradation, and NF-κB DNA binding in the lung after systemic LPS. To block nitric oxide (NO) production, a NO synthase inhibitor was given before L-Arg. LPS induced the production of chemokine protein and mRNA. L-Arg attenuated the production of chemokine protein and mRNA, prevented the decrease in IκB-α levels, and inhibited NF-κB DNA binding. NO synthase inhibition abolished the effects of L-Arg on all measured parameters. Our results suggest that L-Arg abrogates chemokine protein and mRNA production in rat lung after LPS. This effect is dependent on NO and is mediated by stabilization of IκB-α levels and inhibition of NF-κB DNA binding.

Original languageEnglish (US)
Pages (from-to)L400-L408
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume280
Issue number3 24-3
DOIs
StatePublished - Mar 2001

Keywords

  • Acute lung injury
  • Cytokine-induced neutrophil chemoattractant-1
  • Inhibitory factor κB
  • Macrophage inflammatory protein-2
  • Nitric oxide
  • Nitric oxide synthase
  • Nuclear factor-κB

ASJC Scopus subject areas

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

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  • Cite this

    Calkins, C. M., Bensard, D. D., Heimbach, J. K., Meng, X., Shames, B. D., Pulido, E. J., & McIntyre, R. C. (2001). L-Arginine attenuates lipopolysaccharide-induced lung chemokine production. American Journal of Physiology - Lung Cellular and Molecular Physiology, 280(3 24-3), L400-L408. https://doi.org/10.1152/ajplung.2001.280.3.l400