Faculty Collaboration Database

L-arginine attenuates lipopolysaccharide-induced lung chemokine production. Am J Physiol Lung Cell Mol Physiol 2001 Mar;280(3):L400-8

Date

02/13/2001

Pubmed ID

11159022

DOI

10.1152/ajplung.2001.280.3.L400

Scopus ID

2-s2.0-0034998152 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

Chemokines stimulate the influx of leukocytes into tissues. Their production is regulated by nuclear factor-kappaB (NF-kappaB), an inducible transcription factor under the control of inhibitory factor kappaB-alpha (IkappaB-alpha). 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 IkappaB-alpha and preventing NF-kappaB DNA binding. We examined the effect of L-Arg on chemokine production, IkappaB-alpha degradation, and NF-kappaB 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 IkappaB-alpha levels, and inhibited NF-kappaB 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 IkappaB-alpha levels and inhibition of NF-kappaB DNA binding.

Author List

Calkins CM, Bensard DD, Heimbach JK, Meng X, Shames BD, Pulido EJ, McIntyre RC Jr

Author

Casey Matthew Calkins MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arginine
Chemokine CXCL1
Chemokine CXCL2
Chemokines
Chemokines, CXC
Chemotactic Factors
DNA
Growth Substances
I-kappa B Proteins
Intercellular Signaling Peptides and Proteins
Lipopolysaccharides
Lung
Male
NF-kappa B
Nitrates
Nitrites
RNA, Messenger
Rats
Rats, Sprague-Dawley