Skip to main content
SpringerLink
Log in

Niacin inhibits carrageenan-induced neutrophil migration in mice

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Several emerging lines of evidence support an anti-inflammatory role for nicotinic acid (niacin); however, its role in the regulation of leukocyte migration in response to inflammatory stimuli has not been elucidated until now. Herein, we have examined the effect of nicotinic acid on neutrophil recruitment in experimentally induced inflammation. We demonstrated that nicotinic acid treatment inhibited interleukin (IL)-8-induced, leukotriene (LT)B4-induced, and carrageenan-induced neutrophil migration into the pleural cavity of BALB/c mice and reduced neutrophil rolling and adherence in a mouse cremaster muscle preparation. Surprisingly, nicotinic acid treatment increased the level of the neutrophil chemoattractant KC in response to carrageenan. These results suggest that nicotinic acid plays an important role in the regulation of inflammation due to its ability to inhibit the actions of the neutrophil chemoattractants IL-8 and LTB4. Further inhibition of chemoattractants leads to impairment of leukocyte rolling and adherence to the vascular endothelium in the microcirculation of inflamed tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Baggiolini M, Clark-Lewis I (1992) Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett 307:97–101

    Article  PubMed  CAS  Google Scholar 

  • Bhattacharyya S, Gill R, Chen ML, Zhang F, Linhardt RJ, Dudeja PK et al (2008) Toll-like receptor 4 mediates induction of the Bcl10-NFkappaB-interleukin-8 inflammatory pathway by carrageenan in human intestinal epithelial cells. J Biol Chem 283:10550–10558

    Article  PubMed  CAS  Google Scholar 

  • Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S et al (2007) Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis Rheum 56:2829–2839

    Article  PubMed  CAS  Google Scholar 

  • Bruzzone S, Fruscione F, Morando S, Ferrando T, Poggi A, Garuti A et al (2009) Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE. PLoS One 4(11):e7897

    Article  PubMed  Google Scholar 

  • Busso N, Karababa M, Nobile M, Rolaz A, Van Gool F, Galli M, Leo O, So A, De Smedt T (2008) Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD. PLoS One 3(5):e2267

    Article  PubMed  Google Scholar 

  • Byrum RS, Goulet JL, Snouwaert JN, Griffiths RJ, Koller BH (1999) Determination of the contribution of cysteinyl leukotrienes and leukotriene B4 in acute inflammatory responses using 5-lipoxygenase- and leukotriene A4 hydrolase-deficient mice. J Immunol 163:6810–6819

    PubMed  CAS  Google Scholar 

  • Faurschou M, Borregaard N (2003) Neutrophil granules and secretory vesicles in inflammation. Microbes Infect 5:1317–1327

    Article  PubMed  CAS  Google Scholar 

  • Ganji SH, Qin S, Zhang L, Kamanna VS, Kashyap ML (2009) Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis 202:68–75

    Article  PubMed  CAS  Google Scholar 

  • Godin AM, Ferreira WC, Rocha LT, Ferreira RG, Paiva AL, Merlo LA, Nascimento EB Jr, Bastos LF, Coelho MM (2012) Nicotinic acid induces antinociceptive and anti-inflammatory effects in different experimental models. Pharmacol Biochem Behav 101:493–498

    Article  PubMed  CAS  Google Scholar 

  • Gurujeyalakshmi G, Wang Y, Giri SN (2000) Taurine and niacin block lung injury and fibrosis by down-regulating bleomycin-induced activation of transcription nuclear factor-kappaB in mice. J Pharmacol Exp Ther 293:82–90

    PubMed  CAS  Google Scholar 

  • Hageman GJ, Stierum RH (2001) Niacin, poly(ADP-ribose) polymerase-1 and genomic stability. Mutat Res 475:45–56

    Article  PubMed  CAS  Google Scholar 

  • Hickey MJ, Sharkey KA, Sihota EG, Reinhardt PH, Macmicking JD, Nathan C, Kubes P (1997) Inducible nitric oxide synthase-deficient mice have enhanced leukocyte–endothelium interactions in endotoxemia. FASEB J 11:955–964

    PubMed  CAS  Google Scholar 

  • Kirkland JB (2009) Niacin status, NAD distribution and ADP-ribose metabolism. Curr Pharm Des 15:3–11

    Article  PubMed  CAS  Google Scholar 

  • Klein A, Talvani A, Silva PM, Martins MA, Wells TN, Proudfoot A, Luckacs NW, Teixeira MM (2001) Stem cell factor-induced leukotriene B4 production cooperates with eotaxin to mediate the recruitment of eosinophils during allergic pleurisy in mice. J Immunol 167:524–531

    PubMed  CAS  Google Scholar 

  • Kobayashi Y (2008) The role of chemokines in neutrophil biology. Front Biosci 13:2400–2407

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi SD, DeLeo FR (2009) Role of neutrophils in innate immunity: a systems biology-level approach. Wiley Interdiscip Rev Syst Biol Med 1:309–333

    Article  PubMed  CAS  Google Scholar 

  • Kostylina G, Simon D, Fey MF, Yousefi S, Simon HU (2008) Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A). Cell Death Differ 15:134–142

    Article  PubMed  CAS  Google Scholar 

  • Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A 88:4651–4655

    Article  PubMed  CAS  Google Scholar 

  • Kunkel EJ, Jung U, Bullard DC, Norman KE, Wolitzky BA, Vestweber D, Beaudet AL, Ley K (1996) Absence of trauma-induced leukocyte rolling in mice deficient in both P-selectin and intercellular adhesion molecule 1. J Exp Med 183:57–65

    Article  PubMed  CAS  Google Scholar 

  • Kwon WY, Suh GJ, Kim KS, Kwak YH (2011) Niacin attenuates lung inflammation and improves survival during sepsis by downregulating the nuclear factor-kappaB pathway. Crit Care Med 39:328–334

    Article  PubMed  CAS  Google Scholar 

  • Luk T, Malam Z, Marshall JC (2008) Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity. J Leukoc Biol 83:804–816

    Article  PubMed  CAS  Google Scholar 

  • Mathieu J, Tissot M, Nolibe D, Florentin I, Kergonou JF, Giroud JP (1990) Local and systemic effects of an acute inflammation on eicosanoid generation capacity of polymorphonuclear cells and macrophages. Int J Exp Pathol 71:603–616

    PubMed  CAS  Google Scholar 

  • Menezes GB, Rezende RM, Pereira-Silva PE, Klein A, Cara DC, Francischi JN (2008) Differential involvement of cyclooxygenase isoforms in neutrophil migration in vivo and in vitro. Eur J Pharmacol 598:118–122

    Article  PubMed  CAS  Google Scholar 

  • Nagai A, Yasui S, Ozawa Y, Uno H, Konno K (1994) Niacin attenuates acute lung injury induced by lipopolysaccharide in the hamster. Eur Respir J 7:1125–1130

    PubMed  CAS  Google Scholar 

  • Peng Q, Li K, Sacks SH, Zhou W (2009) The role of anaphylatoxins C3a and C5a in regulating innate and adaptive immune responses. Inflamm Allergy Drug Targets 8:236–246

    Article  PubMed  CAS  Google Scholar 

  • Ramos CD, Heluy-Neto NE, Ribeiro RA, Ferreira SH, Cunha FQ (2003) Neutrophil migration induced by IL-8-activated mast cells is mediated by CINC-1. Cytokine 21:214–223

    Article  PubMed  CAS  Google Scholar 

  • Raychaudhuri A, Chertock H, Chovan J, Jones LS, Kimble EF, Kowalski TJ, Peppard J, White DH, Satoh Y, Roland D (1997) Inhibition of LTB4 biosynthesis in situ by CGS 23885, a potent 5-lipoxygenase inhibitor, correlates with its pleural fluid concentrations in an experimentally induced rat pleurisy model. Naunyn Schmiedebergs Arch Pharmacol 355:470–474

    Article  PubMed  CAS  Google Scholar 

  • Rongvaux A, Andris F, Van Gool F, Leo O (2003) Reconstructing eukaryotic NAD metabolism. Bioessays 25:683–690

    Article  PubMed  CAS  Google Scholar 

  • Samuelsson B (1983) Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 220:568–575

    Article  PubMed  CAS  Google Scholar 

  • Seo SM, McIntire LV, Smith CW (2001) Effects of IL-8, Gro-alpha, and LTB(4) on the adhesive kinetics of LFA-1 and Mac-1 on human neutrophils. Am J Physiol Cell Physiol 281(C1):568–578

    Google Scholar 

  • Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K (2003) Molecular identification of nicotinic acid receptor. Biochem Biophys Res Commun 303:364–369

    Article  PubMed  CAS  Google Scholar 

  • Szabo C, Lim LH, Cuzzocrea S, Getting SJ, Zingarelli B, Flower RJ et al (1997) Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts antiinflammatory effects. J Exp Med 186:1041–1049

    Article  PubMed  CAS  Google Scholar 

  • Tavintharan S, Lim SC, Sum CF (2009) Effects of niacin on cell adhesion and early atherogenesis: biochemical and functional findings in endothelial cells. Basic Clin Pharmacol Toxicol 104:206–210

    Article  PubMed  CAS  Google Scholar 

  • Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S (2003) PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 9:352–355

    Article  PubMed  CAS  Google Scholar 

  • Van Gool F, Galli M, Gueydan C, Kruys V, Prevot PP, Bedalov A, Mostoslavsky R, Alt FW, De Smedt T, Leo O (2009) Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner. Nat Med 15:206–210

    Article  PubMed  Google Scholar 

  • Vicaut E, Stucker O (1990) An intact cremaster muscle preparation for studying the microcirculation by in vivo microscopy. Microvasc Res 39:120–122

    Article  PubMed  CAS  Google Scholar 

  • Wang QJ, Giri SN, Hyde DM, Nakashima JM, Javadi I (1990) Niacin attenuates bleomycin-induced lung fibrosis in the hamster. J Biochem Toxicol 5:13–22

    Article  PubMed  CAS  Google Scholar 

  • Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376

    Article  PubMed  CAS  Google Scholar 

  • Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB (2003) Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem 278:9869–9874

    Article  PubMed  CAS  Google Scholar 

  • Yang XD, Corvalan JR, Wang P, Roy CM, Davis CG (1999) Fully human anti-interleukin-8 monoclonal antibodies: potential therapeutics for the treatment of inflammatory disease states. J Leukoc Biol 66:401–410

    PubMed  CAS  Google Scholar 

  • Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu TA (1997) G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature 387:620–624

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) and Conselho Nacional de Pesquisa e Desenvolvimento (CNPq), Brazil. The authors are grateful to W.G. Pimenta for his excellent technical assistance. R.G.F., A.M.G., and L.F.G. are graduate student fellows from CAPES, Brazil.

Conflict of interest

The authors declare they have no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratory of Inflammation and Pain, Institute of Biological Sciences, UFMG, Belo Horizonte, Brazil

    Raphael Gomes Ferreira, Tamires Cardoso Matsui, Lindisley Ferreira Gomides & André Klein

  2. Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, UFMG, Belo Horizonte, Brazil

    Adriana Martins Godin & Márcio de Matos Coelho

  3. Department of Morphology, Institute of Biological Sciences, UFMG, Belo Horizonte, Brazil

    Gustavo Batista Menezes

  4. Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, 6627 Pampulha, Belo Horizonte, MG, Brazil

    André Klein

Authors
  1. Raphael Gomes Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamires Cardoso Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lindisley Ferreira Gomides
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adriana Martins Godin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gustavo Batista Menezes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Márcio de Matos Coelho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. André Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to André Klein.

Electronic supplementary material

(MPEG 648 kb)

(MPEG 690 kb)

(MPEG 514 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferreira, R.G., Matsui, T.C., Gomides, L.F. et al. Niacin inhibits carrageenan-induced neutrophil migration in mice. Naunyn-Schmiedeberg's Arch Pharmacol 386, 533–540 (2013). https://doi.org/10.1007/s00210-013-0854-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-013-0854-3

Keywords

Search

Navigation