L-Arginine attenuates lipopolysaccharide-induced lung chemokine production

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.