PMID- 26769828 OWN - NLM STAT- MEDLINE DCOM- 20161024 LR - 20161230 IS - 1899-1505 (Electronic) IS - 0867-5910 (Linking) VI - 66 IP - 6 DP - 2015 Dec TI - Immunomodulatory effect of riboflavin deficiency and enrichment - reversible pathological response versus silencing of inflammatory activation. PG - 793-802 AB - Ariboflavinosis, that is, vitamin B2 deficiency, is a common problem affecting the populations of both developing and affluent countries. Teenagers, elderly people, pregnant women, and alcohol abusers represent groups that are particularly susceptible to this condition. This study was aimed to determine the effect of different riboflavin concentrations (deficiency and supplementation) on macrophages response induced by bacteria or yeast-derived factors i.e. lipopolysaccharide (LPS) and zymosan, respectively. Mouse macrophage RAW 264.7 cells were cultured for 5 days in a medium with a riboflavin concentration corresponding to moderate riboflavin deficiency (3.1 nM), physiological state (10.4 nM), or vitamin pill supplementation (300 nM). On the third or fourth day of deprivation, the medium in some groups was supplemented with riboflavin (300 nM). Macrophages activation were assessed after LPS or zymosan stimulation. Short-term (5 days) riboflavin deprivation resulted in the pathological macrophages activation, manifested especially in a reduction of cell viability and excess release of tumor necrosis factor-alpha (TNF-alpha) and high-mobility group box 1 (HMGB1) protein. Moreover, the levels of inducible nitric oxide synthase (iNOS), nitric oxide (NO), heat shock protein (Hsp72), interleukin 1beta (IL-1beta), monocyte chemoattractant protein-1 (MCP-1), and interleukin 10 (IL-10) decreased after riboflavin deprivation, but medium enrichment with riboflavin (300 nM) on the third or fourth day reversed this effect. In the riboflavin-supplemented group, LPS-stimulated macrophages showed lower mortality accompanied by higher Hsp72 expression, reduction of Toll-like receptor 4 (TLR4) and TNF-alpha, and elevation of NO, IL-6, and IL-10. Moreover, the TLR6, NO, iNOS, IL-1beta, MCP-1, and the keratinocyte chemoattractant (KC) levels significantly decreased in the zymosan-stimulated groups maintained in riboflavin-enriched medium. We conclude that short-term riboflavin deficiency significantly impairs the ability of macrophages to induce proper immune response, while riboflavin enrichment decreases the proinflammatory activation of macrophages. FAU - Mazur-Bialy, A I AU - Mazur-Bialy AI AD - Department of Ergonomics and Exercise Physiology, Faculty of Health Science, Jagiellonian University Medical College, Cracow, Poland. agnieszka.mazur@uj.edu.pl. FAU - Pochec, E AU - Pochec E AD - Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Cracow, Poland. FAU - Plytycz, B AU - Plytycz B AD - Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, Cracow, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Poland TA - J Physiol Pharmacol JT - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JID - 9114501 RN - 0 (Cytokines) RN - 0 (HSP72 Heat-Shock Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Nitrites) RN - 0 (Toll-Like Receptors) RN - 9010-72-4 (Zymosan) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) SB - IM MH - Animals MH - Cell Line MH - Cytokines/genetics/immunology MH - HSP72 Heat-Shock Proteins/immunology MH - Lipopolysaccharides MH - Macrophages/drug effects/*immunology MH - Mice MH - NF-kappa B/immunology MH - Nitric Oxide Synthase Type II/immunology MH - Nitrites/immunology MH - Riboflavin Deficiency/*immunology MH - Toll-Like Receptors/genetics/immunology MH - Zymosan EDAT- 2016/01/16 06:00 MHDA- 2016/10/25 06:00 CRDT- 2016/01/16 06:00 PHST- 2015/06/30 00:00 [received] PHST- 2015/12/04 00:00 [accepted] PHST- 2016/01/16 06:00 [entrez] PHST- 2016/01/16 06:00 [pubmed] PHST- 2016/10/25 06:00 [medline] PST - ppublish SO - J Physiol Pharmacol. 2015 Dec;66(6):793-802.