Skip to main content

Advertisement

SpringerLink
Log in

Amino acids exhibit anti-inflammatory effects in human monocytic leukemia cell line, THP-1 cells

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

The elemental diet is one of the effective therapies for inflammatory bowel disease. However, the mechanism remains unclear, and there have never been reports about the inhibitory effects of amino acids in human monocytes/macrophages. We investigated the inhibitory effects of amino acids on cytokine production or expression of adhesion molecules that are involved in inflammatory diseases, in human monocytes/macrophages.

Methods

We examined the inhibitory effects of cysteine, histidine or glycine on the induction of nuclear factor-κB (NF-κB) activation, expression of intracellular adhesion molecule-1 (ICAM-1, CD54) and production of interleukin-8 (IL-8) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs) stimulated with tumor necrosis factor-α (TNF-α).

Results

Cysteine, histidine and glycine significantly reduced the activation of NF-κB in THP-1 cells stimulated with TNF-α. In addition, cysteine and histidine significantly inhibited the expression of ICAM-1 and production of IL-8 in THP-1 cells and PBMCs.

Conclusions

Our results suggest that cysteine and histidine exhibit anti-inflammatory effects in THP-1 cells, and may be responsible for the efficacy of treatment in inflammatory bowel diseases.

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

  1. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–34.

    Article  PubMed  CAS  Google Scholar 

  2. Himmel ME, Hardenberg G, Piccirillo CA, Steiner TS, Levings MK. The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease. Immunology. 2008;125:145–53.

    Article  PubMed  CAS  Google Scholar 

  3. Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007;117:514–21.

    Article  PubMed  CAS  Google Scholar 

  4. Zhou L, Braat H, Faber KN, Dijkstra G, Peppelenbosch MP. Monocytes and their pathophysiological role in Crohn’s disease. Cell Mol Life Sci. 2009;66:192–202.

    Article  PubMed  CAS  Google Scholar 

  5. Brown SJ, Mayer L. The immune response in inflammatory bowel disease. Am J Gastroenterol. 2007;102:2058–69.

    Article  PubMed  CAS  Google Scholar 

  6. Sanchez-Munoz F, Dominguez-Lopez A, Yamamoto-Furusho JK. Role of cytokines in inflammatory bowel disease. World J Gastroenterol. 2008;14:4280–8.

    Article  PubMed  CAS  Google Scholar 

  7. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627–40.

    Article  PubMed  CAS  Google Scholar 

  8. Rutgeerts P, D’Haens G, Targan S, Vasiliauskas E, Hanauer SB, Present DH, Mayer L, Van Hogezand RA, Braakman T, DeWoody KL, Scaible TF, Van Deventer SJ. Efficiency and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology. 1999;117:761–9.

    Article  PubMed  CAS  Google Scholar 

  9. D’haens G, Van Deventer S, Van Hogezand R, Chalmers D, Kothe C, Baert F, Braakman T, Schaible T, Geboes K, Rutgeerts P. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn’s disease: a European multicenter trial. Gastroenterology. 1999;116:1029–34.

    Article  PubMed  Google Scholar 

  10. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ. Infliximab for treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340:1398–405.

    Article  PubMed  CAS  Google Scholar 

  11. Sandborn WJ, Feagan BG, Hanauer SB, Present DH, Sutherland LR, Kamm MA, Wolf DC, Baker JP, Hawkey C, Archambault A, Bernstein CN, Novak C, Heath PK, Targan SR. An engineered human antibody to TNF (CDP571) for active Crohn’s disease: a randomized double-blind placebo-controlled trial. Gastroenterology. 2001;120:1330–8.

    Article  PubMed  CAS  Google Scholar 

  12. Collart MA, Baeuerle P, Vassalli P. Regulation of tumor necrosis factor alpha transcription in macrophages: Involvement of four κB-like motifs and of constitutive and inducible forms of NF-κB. Mol Cell Biol. 1990;10:1498–506.

    PubMed  CAS  Google Scholar 

  13. Libermann TA, Baltimore D. Activation interleukin-6 gene expression through the NF-κB transcription factor. Mol Cell Biol. 1990;10:2327–34.

    PubMed  CAS  Google Scholar 

  14. Chen CC, Rosenbloom CL, Anderson DC, Manning AM. Selective inhibition of E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1 expression by inhibitors of IκB-α phosphorylation. J Immunol. 1995;155:3538–45.

    PubMed  CAS  Google Scholar 

  15. Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T, Akira S. Transcription factors NF-IL6 and NK-κB synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci USA. 1993;90:10193–7.

    Article  PubMed  CAS  Google Scholar 

  16. Kunsch C, Lang RK, Rosen CA, Shannon MF. Synergistic transcriptional activation of the IL-8 gene by NF-κB p65 (RelA) and NF-IL-6. J Immunol. 1994;153:153–64.

    PubMed  CAS  Google Scholar 

  17. Mukaida N, Mahe Y, Matsushima K. Cooperative interaction of nuclear factor-κB- and cis-regulatory enhancer binding protein-like factor binding elements in activating the interleukin-8 gene by pro-inflammatory cytokines. J Biol Chem. 1990;265:21128–33.

    PubMed  CAS  Google Scholar 

  18. Ueda A, Ishigatsubo Y, Okubo T, Yoshimura T. Transcriptional regulation of the human monocyte chemoattractant protein-1 gene. J Biol Chem. 1997;272:31092–9.

    Article  PubMed  CAS  Google Scholar 

  19. Faffe DS, Whitehead T, Moore PE, Baraldo S, Flynt L, Bourgeois K, Panettieri RA, Shore SA. IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role for IL-4 genotype. Am J Physiol Lung Cell Mol Physiol. 2003;285:907–14.

    Google Scholar 

  20. Sekiya T, Tsunemi Y, Miyamasu M, Ohta K, Morita A, Saeki H, Matsushima K, Yoshie O, Tsuchiya N, Yamaguchi M, Yamamoto K, Tamaki K, Hirai K. Variations in the human TH2-specific chemokine TARC gene. Immunogenetics. 2003;54:742–5.

    PubMed  CAS  Google Scholar 

  21. Tsune I, Ikejima K, Hirose M, Yoshikawa M, Enomoto N, Takei Y, Sato N. Dietary glycine prevents chemical-induced experimental colitis in the rat. Gastroenterology. 2003;125:775–85.

    Article  PubMed  CAS  Google Scholar 

  22. Andou A, Hisamatsu T, Okamoto S, Chinen H, Kamada N, Kobayashi T, Hashimoto M, Okutsu T, Shimbo K, Takeda T, Matsumoto H, Sato A, Ohtsu H, Suzuki M, Hibi T. Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophage. Gastroenterology. 2009;136:564–74.

    Article  PubMed  CAS  Google Scholar 

  23. Son DO, Satsu H, Shimizu M. Histidine inhibits oxidative stress- and TNF-α-induced interleukin-8 secretion in intestinal epithelial cells. FEBS Lett. 2005;579:4671–7.

    Article  PubMed  CAS  Google Scholar 

  24. Wheeler MD, Thurman R. Production of superoxide and TNF-α from alveolar macrophages is blunted by glycine. Am J Physiol. 1999;277:L952–9.

    PubMed  CAS  Google Scholar 

  25. Stachlewitz RF, Li X, Smith S, Bunzendahl H, Graves LM, Thurman RG. Glycine inhibits growth of T lymphocytes by an IL-2-independent mechanism. J Immunol. 2000;164:176–82.

    PubMed  CAS  Google Scholar 

  26. Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG. Dietary glycine prevents peptidoglycan-polysaccharide-induced reactive arthritis in the rats: role for glycine-gated chloride channel. Infect Immun. 2001;69:5883–91.

    Article  PubMed  CAS  Google Scholar 

  27. Wheeler MD, Rose ML, Yamashima S, Enomoto N, Seabra V, Madren J, Therman RG. Dietary glycine blunts lung inflammatory cell influx following acute endotoxin. Am J Physiol Lung Cell Mol Physiol. 2000;279:L390–8.

    PubMed  CAS  Google Scholar 

  28. Liboni KC, Li N, Scumpia PO, Neu J. Glutamine modulates LPS-induced IL-8 production through IκB/NF-κB in fetal and adult intestinal epithelium. J Nutr. 2005;135:245–51.

    PubMed  CAS  Google Scholar 

  29. Yamamoto T, Nakahigashi M, Umegae S. Impact of elemental diet on mucosal inflammation in patients with active Crohn’s disease. Cytokine production and endoscopic and histological findings. Inflamm Bowel Dis. 2005;11:580–8.

    Article  PubMed  Google Scholar 

  30. Kim CJ, Kovacs-Nolan J, Yang C, Archbold T, Fan MZ, Mine Y. l-cysteine supplementation attenuates local inflammation and restores gut homeostasis in porcine model of colitis. Biochim Biophys Acta. 2009;1790:1161–9.

    PubMed  CAS  Google Scholar 

  31. Auwerx J. The human leukemia cell line, THP-1: a multifaceted model for the study of monocyte-macrophage differetiation. Experientia. 1991;47:22–31.

    Article  PubMed  CAS  Google Scholar 

  32. Renard P, Ernest I, Houbion A, Art M, Le Calvez H, Raes M, Remacle J. Development of a sensitive multi-well colorimetric assay for active NF-κB. Nucleic Acids Res. 2001;29:e21.

    Article  PubMed  CAS  Google Scholar 

  33. Ichiyama T, Nishikawa M, Yoshitomi T, Hasegawa S, Matsubara T, Hayashi T, Furukawa S. Clarithromycin inhibits NF-kappaB activation in human peripheral blood mononuclear cells and pulmonary epithelial cells. Antimicrob Agents Chemother. 2001;45:44–7.

    Article  PubMed  CAS  Google Scholar 

  34. Yoneshima Y, Ichiyama T, Ayukawa H, Matsubara T, Furukawa S. Fosfomycin inhibits NF-kappaB activation in U-937 and Jurkat cells. Int J Antimicrob Agents. 2003;21:589–92.

    Article  PubMed  CAS  Google Scholar 

  35. Umeda M, Ichiyama T, Hasegawa S, Kaneko M, Matsubara T, Furukawa S. Theophylline inhibits NF-kappaB activation in human peripheral blood mononuclear cells. Int Arch Allergy Immunol. 2002;128:130–5.

    Article  PubMed  CAS  Google Scholar 

  36. Ichiyama T, Hasegawa S, Matsubara T, Hayashi T, Furukawa S. Theophylline inhibits NF-κB activation and IκBα degradation in human pulmonary epithelial cells. Naunyn-Schmiedeberg’s Arch Pharmacol. 2001;364:558–61.

    Article  CAS  Google Scholar 

  37. Ichiyama T, Hasegawa S, Umeda M, Terai K, Matsubara T, Furukawa S. Pranlukast inhibits NF-kappa B activation in human monocytes/macrophages and T cells. Clin Exp Allergy. 2003;33:802–7.

    Article  PubMed  CAS  Google Scholar 

  38. Ichiyama T, Ueno Y, Hasegawa M, Niimi A, Matsubara T, Furukawa S. Intravenous immunoglobulin inhibits NF-κB activation and affects Fcγ receptor expression in monocytes/macrophages. Naunyn-Schmiederberg’s Arch Pharmacol. 2004;369:428–33.

    Article  CAS  Google Scholar 

  39. Ichiyama T, Ueno Y, Isumi H, Niimi A, Matsubara T, Furukawa S. An immunoglobulin agent (IVIG) inhibits NF-κB activation in cultured endothelial cells of coronary arteries in vitro. Inflamm Res. 2004;53:253–6.

    Article  PubMed  CAS  Google Scholar 

  40. Kim CJ, Kovacs-Nolan JA, Yang C, Archbold T, Fan MZ, Mine Y. l-Tryptophan exhibits therapeutic function in a porcine model of dextran sodium sulfate (DSS)-induced colitis. J Nutr Biochem. 2010;21:468–75.

    Google Scholar 

  41. Wheeler MD, Ikejema K, Enomoto N, Stacklewitz RF, Seabra V, Zhong Z, Yin M, Schemmer P, Rose ML, Rusyn I, Bradford B, Thurman RG. Glycine: a new anti-inflammatory immunonutrient. Cell Mol Life Sci. 1999;56:843–56.

    Article  PubMed  CAS  Google Scholar 

  42. Ukeda H, Hasegawa Y, Harada Y, Sawamura M. Effect of carnosine and related compounds on the inactivation of human Cu, Zn-superoxide dismutase by modification of fructose and glycolaldehyde. Biosci Biotechnol Biochem. 2002;66:36–43.

    Article  PubMed  CAS  Google Scholar 

  43. Guiotto A, Calderan A, Ruzza P, Borin G. Carnosine and carnosine-related antioxidants: a review. Curr Med Chem. 2005;12:2293–315.

    Article  PubMed  CAS  Google Scholar 

  44. Yan SL, Wu ST, Yin MC, Chen HT, Chen HC. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. J Food Sci. 2009;74:H259–65.

    Article  PubMed  CAS  Google Scholar 

  45. O’Hara AM, Bhattacharyya A, Bai J, Mifflin RC, Ernst PB, Mitra S, Crowe SE. Tumor necrosis factor (TNF)-alpha-induced IL-8 expression in gastric epithelial cells: role of reactive oxygen species and AP endonuclease-1/redox factor (Ref)-1. Cytokine. 2009;46:359–69.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by Morinaga Hoshi-kai to S. Hasegawa. All authors have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan

    Shunji Hasegawa, Takashi Ichiyama, Ayami Ohsaki, Reiji Hirano, Yasuhiro Haneda, Reiji Fukano & Susumu Furukawa

  2. Marketing Department, Ajinomoto Pharma Co., Ltd., 1-15-1 Kyobashi, Chuo-ku, Tokyo, 104-8315, Japan

    Ichiro Sonaka

  3. Faculty of Human Life Sciences, Department of Food and Health Sciences, Jissen Women’s University, 4-1-1 Ohsakaue, Hino, Tokyo, 191-8510, Japan

    Masami Hara & Susumu Furukawa

Authors
  1. Shunji Hasegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Ichiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ichiro Sonaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayami Ohsaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Reiji Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasuhiro Haneda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Reiji Fukano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masami Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Susumu Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shunji Hasegawa.

Additional information

Responsible Editor: Makoto Katori.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hasegawa, S., Ichiyama, T., Sonaka, I. et al. Amino acids exhibit anti-inflammatory effects in human monocytic leukemia cell line, THP-1 cells. Inflamm. Res. 60, 1013–1019 (2011). https://doi.org/10.1007/s00011-011-0362-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-011-0362-1

Keywords

Search

Navigation