Niacin inhibits carrageenan-induced neutrophil migration in mice

Ferreira, Raphael Gomes; Matsui, Tamires C.; Gomides, Lindisley Ferreira; Godin, Adriana M.; Menezes, Gustavo B.; Coelho, Márcio de Matos; Klein, André

doi:10.1007/s00210-013-0854-3

Cited by 13 publications

(7 citation statements)

References 39 publications

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“…Evidences point out to impairment of neutrophil recruitment due to elastase inhibition, but more studies are required to confirm this hypothesis. Our findings have a strong impact on drug development that inhibit neutrophil migration and it may represent an important new therapeutic strategy for treatment of inflammatory diseases [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni SmKI-1 serine protease inhibitor binds to elastase and impairs neutrophil function and inflammation

et al. 2018

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Protease inhibitors have important function during homeostasis, inflammation and tissue injury. In this study, we described the role of Schistosoma mansoni SmKI-1 serine protease inhibitor in parasite development and as a molecule capable of regulating different models of inflammatory diseases. First, we determine that recombinant (r) SmKI-1 and its Kunitz domain but not the C-terminal region possess inhibitory activity against trypsin and neutrophil elastase (NE). To better understand the molecular basis of NE inhibition by SmKI-1, molecular docking studies were also conducted. Docking results suggest a complete blockage of NE active site by SmKI-1 Kunitz domain. Additionally, rSmKI-1 markedly inhibited the capacity of NE to kill schistosomes. In order to further investigate the role of SmKI-1 in the parasite, we designed specific siRNA to knockdown SmKI-1 in S. mansoni. SmKI-1 gene suppression in larval stage of S. mansoni robustly impact in parasite development in vitro and in vivo. To determine the ability of SmKI-1 to interfere with neutrophil migration and function, we tested SmKI-1 anti-inflammatory potential in different murine models of inflammatory diseases. Treatment with SmKI-1 rescued acetaminophen (APAP)-mediated liver damage, with a significant reduction in both neutrophil recruitment and elastase activity. In the model of gout arthritis, this protein reduced neutrophil accumulation, IL-1β secretion, hypernociception, and overall pathological score. Finally, we demonstrated the ability of SmKI-1 to inhibit early events that trigger neutrophil recruitment in pleural cavities of mice in response to carrageenan. In conclusion, SmKI-1 is a key protein in S. mansoni survival and it has the ability to inhibit neutrophil function as a promising therapeutic molecule against inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni SmKI-1 serine protease inhibitor binds to elastase and impairs neutrophil function and inflammation

et al. 2018

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“…In another study, niacin was shown to reduce liver cholesteryl ester transfer protein (CETP) expression via its effects on reducing hepatic macrophage [57]. Niacin inhibited carrageenan-activated neutrophil migration in mice further suggesting its anti-inflammatory role through mechanisms involving alterations in chemoattraction [58]. Niacin signals through GPR109A, the same receptor as the short chain fatty acid (SCFA), butyrate.…”

Section: Niacin B3mentioning

confidence: 99%

B Vitamins and Their Role in Immune Regulation and Cancer

et al. 2020

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B group vitamins represent essential micronutrients for myriad metabolic and regulatory processes required for human health, serving as cofactors used by hundreds of enzymes that carry out essential functions such as energy metabolism, DNA and protein synthesis and other critical functions. B vitamins and their corresponding vitamers are universally essential for all cellular life forms, from bacteria to humans. Humans are unable to synthesize most B vitamins and are therefore dependent on their diet for these essential micronutrients. More recently, another source of B vitamins has been identified which is derived from portions of the 1013 bacterial cells inhabiting the gastrointestinal tract. Here we review the expanding literature examining the relationship between B vitamins and the immune system and diverse cancers. Evidence of B vitamin’s role in immune cell regulation has accumulated in recent years and may help to clarify the disparate findings of numerous studies attempting to link B vitamins to cancer development. Much work remains to be carried out to fully clarify these relationships as the complexity of B vitamins’ essential functions complicates an unequivocal assessment of their beneficial or detrimental effects in inflammation and cancers.

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“…[2][3][4] The immunosuppressive effects 3 are Niacr1-mediated and disappear in Niacr1 −/− mutant mice. In rodents, 0.4 g per day, 2 2.2 g per day, 3 or 2.9 g per day 4 (human-equivalent dose) of niacin induces immunosuppressive regulatory T cells 3 ; increases the circulating levels of immunosuppressive interleukin-10 3 ; inhibits macrophage differentiation and migration, 3 neutrophil migration, 4 and leukocyte adhesion 4 ; reduces circulating levels of proinflammatory interleukin-17, 3 high-mobility group B box 1, 2 and matrix metalloproteinase 9 2 ; and suppresses clinical inflammation.…”

Section: Doi: 101056/nejmc1411240mentioning

confidence: 99%

“…From the placebo group of our recent (2011 to 2013) randomized, controlled trial in Uganda, 4 we quantified parasite-clearance kinetics using identical methods (standardized parasite-clearance estimator) 5 among 91 children with severe falciparum malaria treat-ed with intravenous artesunate. This and other studies 2,3 included patients with uncomplicated malaria, whereas young children with severe malaria in Africa represent a key population of interest with the highest mortality burden.…”

Section: Spread Of Artemisinin Resistance In Malariamentioning

confidence: 99%