l-Arginine attenuates lipopolysaccharide-induced lung chemokine production.
Calkins, Casey M., Denis D. Bensard, Julie K. Heimbach, Xianzhong Meng, Brian D.
Shames, Edward J. Pulido, and Robert C. McIntyre, Jr.
1Department of Surgery, University of Colorado Health Sciences Center and The
Veterans Affairs Hospital, Denver 80262; and 2Department of Pediatric Surgery, The
Children's Hospital, Denver, Colorado
APStracts 7:0266L, 2000.
Chemokines stimulate the influx of leukocytes into tissues. Their production is regulated
by nuclear factor-?B (NF-?B), an inducible transcription factor under the control of
inhibitory factor ?B-a (I?B-a). 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 I?B-a and preventing NF-?B DNA binding. We
examined the effect of l-Arg on chemokine production, I?B-a degradation, and NF-?B
DNA binding in the lung after systemic LPS. To block nitric oxide (NO) production, a
NO synthase inhibitor was given before the 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 I?B-a levels, and inhibited NF-?B 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 I?B-a levels and
the inhibition of NF-?B DNA binding.
Received 8 May 2000; accepted in final form 20 September 2000
APS Manuscript Number L150-0.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 30 November 2000