Signalling mechanisms involved in the induction of inducible nitric oxide synthase by Lactobacillus rhamnosus GG, endotoxin, and lipoteichoic acid

Background and Aims: Probiotic Lactobacillus rhamnosus GG (Lactobacillus GG) has been found beneficial in the treatment of viral and antibiotic-associated diarrhea. Recently, it has also been shown to induce nitric oxide (NO) production, and have some other immunostimulatory effects. The aim of the present study was to investigate the mechanisms involved in the induction of inducible nitric oxide synthase (iNOS) and NO production by Lactobacillus GG. Methods and Results: iNOS expression and NO production induced by Lactobacillus GG, lipopolysaccharide (LPS), and lipoteichoic acid (LTA) was abrogated by NOS inhibitors L-NMMA and 1400W, by a protein synthesis inhibitor cycloheximide, by a tyrosine kinase inhibitor genistein and by a NF-kappaB inhibitor pyrrolidinedithiocarbamate (PDTC) in J774 macrophages. Polymyxin B inhibited NO production induced by LPS, but did not inhibit Lactobacillus GG induced NO production. (P)42/44 MAP-kinase inhibitor PD98059, dexamethasone and cyclosporine A inhibited partially iNOS protein expression and NO formation in Lactobacillus GG, LPS and LTA treated cells. Ro 31-8220 (protein kinase C inhibitor) and SB203580 (p38 MAP-kinase inhibitor) had only a minor effect on NO production. Conclusions: Lactobacillus GG induced NO production through iNOS pathway and the mechanisms mediating that process were very similar with those involved in LPS and LTA induced NO synthesis.