Signal transduction pathways of IL-1β-mediated iNOS in pulmonary vascular smooth muscle cells

Jonathan Finder, Jennifer L. Petrus, Andrew Hamilton, Raphael T. Villavicencio, Bruce R. Pitt, Saïd M. Sebti

Research output: Contribution to journalArticle

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Abstract

Interleukin (IL)-1β is an important early mediator of inflammation in pulmonary artery smooth muscle cells. We previously reported that a geranylgeranyltransferase inhibitor elevated basal levels of inducible nitric oxide synthase (iNOS) and enhanced IL-1β-mediated induction, suggesting that Rac or Rho small G proteins are candidates for antagonism of such induction. In this study, overexpression of constitutively active Rac1 or its dominant negative mutant did not affect IL-1β induction of iNOS. Alternatively, treatment with Clostridium botulinum C3 exoenzyme, which ADP-ribosylates Rho, was associated with superinduction of iNOS, suggesting an inhibitory role for Rho. IL-1β activated the three mitogen-activated protein kinase (extracellular signal-regulated kinases 1 and 2, c-Jun NH2-terminal kinase/stress-activated protein kinase, and p38) and the Janus kinase (JAK)-signal transducer and activator of transcription pathways. The former two pathways were not associated with IL-1β-mediated iNOS induction, whereas the latter two appeared to have inhibitory roles in iNOS expression. These data suggest that a broad intracellular signaling response to IL-1β in rat pulmonary artery smooth muscle cells results in elevated levels of iNOS that is opposed by the geranylgeranylated small G protein Rho as well as the p38 and JAK2 pathways.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number4 25-4
StatePublished - Oct 20 2001
Externally publishedYes

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Nitric Oxide Synthase Type II
Interleukin-1
Vascular Smooth Muscle
Smooth Muscle Myocytes
Signal Transduction
Lung
Monomeric GTP-Binding Proteins
Pulmonary Artery
Janus Kinases
Inflammation Mediators
rho GTP-Binding Proteins
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Heat-Shock Proteins
Mitogen-Activated Protein Kinases
Transducers
Adenosine Diphosphate
Protein Kinases

All Science Journal Classification (ASJC) codes

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

Cite this

Signal transduction pathways of IL-1β-mediated iNOS in pulmonary vascular smooth muscle cells. / Finder, Jonathan; Petrus, Jennifer L.; Hamilton, Andrew; Villavicencio, Raphael T.; Pitt, Bruce R.; Sebti, Saïd M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 281, No. 4 25-4, 20.10.2001.

Research output: Contribution to journalArticle

Finder, Jonathan ; Petrus, Jennifer L. ; Hamilton, Andrew ; Villavicencio, Raphael T. ; Pitt, Bruce R. ; Sebti, Saïd M. / Signal transduction pathways of IL-1β-mediated iNOS in pulmonary vascular smooth muscle cells. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2001 ; Vol. 281, No. 4 25-4.
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