Vitamin B6 suppresses NF-kappaB activation in LPS-stimulated mouse macrophages.
Although vitamin B6 has been supposed to have anti-inflammatory effects, the molecular mechanism is not fully understood. To explore the mechanism of anti-inflammatory effects of vitamin B6, we have examined the effect of vitamin B6 on lipopolysaccharide (LPS)-stimulated inflammatory response in RAW 264.7 macrophages. This study demonstrated that vitamin B6 (pyridoxal) pretreatment of RAW cells inhibited LPS-induced expression of iNOS and COX-2 at the mRNA and protein levels. Vitamin B6 inhibited LPS-induced nuclear translocation of the NF-kappaB, the proinflammatory transcription factor, with reduction of the extent of LPS-induced IkappaBalpha degradation in RAW cells. Although vitamin B6 did not affect cellular proteasome activity, in vitro phosphorylation analysis with glutathione S-transferase-fused IkappaBalpha has shown that vitamin B6 suppressed LPS-induced IkappaB kinase activation. Furthermore, we demonstrated that elevating dietary vitamin B6 suppressed NO production in vivo in response to LPS administration. These observations suggest that the anti-inflammatory effect of vitamin B6 is mediated by suppression of NF-kappaB activation.
Yanaka
Noriyuki
N
Department of Bioresource Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
Koyama
Taka-Aki
TA
Komatsu
Shun-Ichiro
S
Nakamura
Eri
E
Kanda
Mayumi
M
Kato
Norihisa
N
D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011730:Pyridoxal / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D025101:Vitamin B 6 / Q000494:pharmacology*
D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D011730:Pyridoxal; D025101:Vitamin B 6; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D046988:Proteasome Endopeptidase Complex