Skip to main content
SpringerLink
Log in

Phytic Acid Modulates In Vitro IL-8 and IL-6 Release from Colonic Epithelial Cells Stimulated with LPS and IL-1β

  • Original Paper
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Phytic acid (PA), a major fiber-associated component of wheat bran and legumes, is physiologically present in the human large gut. The aim of this study was to examine the role of PA in immunologic function of intestinal epithelial cells by analyzing its effect on interleukin (IL)-8 and IL-6 secretion by colonocytes and its role in the response of these cells to bacterial lipopolysaccharides (LPS) and IL-1β. The human colon cell line Caco-2 was exposed to LPS isolated from two strains of Desulfovibrio desulfuricans, wild intestinal and type soil strains, as well as to LPS from E. coli. Cells were also treated with IL-1β and with a combination of LPS and IL-1β. PA had a suppressive effect on IL-8 basal release and it dose dependently reduced IL-8 secretion by colonocytes stimulated with LPS and IL-1β. On the contrary, PA increased constitutive IL-6 secretion and exhibited differentiated effects on LPS responsiveness of cells depending on its concentration and LPS origin. PA was also an efficient down-regulator of IL-6 secretion stimulated by binary actions of LPS and IL-1β. The ability of PA to modulate IL-8 and IL-6 release suggests that PA present in the intestinal milieu may exert immunoregulatory effects on colonic epithelium under physiological conditions or during microbe-induced infection/inflammation in order to maintain the colonic mucosa in a noninflammatory state or to counteract infection.

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. Fujihashi K, Ernst PB (1999) A mucosal internet. Epithelial cell-immune cell interactions. In: Ogra PL, Mestecky J, Lamm ME, Strober W, Bienenstock J, McGhee JR (eds) Mucosal immunology. Academic Press, New York, pp 623–624

    Google Scholar 

  2. Jung HC, Eckmann L, Yang S, Panja A, Fierer J, Morzycka-Wroblewska E, Kagnoff MF (1995) A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest 95:55–65

    Article  PubMed  CAS  Google Scholar 

  3. Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemotactic cytokines-CXC and CC chemokines. Adv Immunol 55:97–179

    PubMed  CAS  Google Scholar 

  4. Izutani R, Loh E, Reinecker HC, Ohno Y, Fusunyan RD, Lichtenstein GR, Rombeau JL, MacDermott RP (1995) Increased expression of interleukin-8 mRNA in ulcerative colitis and Crohn’disease mucosa and epithelial cells. Inflam Bowel Dis 1:37–47

    Article  Google Scholar 

  5. Akira S, Hirano T, Taga T, Kishimito T (1999) Biology of multifunctional cytokines: IL-6 and related molecules (IL 1 and TNF). FASEB J 4:2860–2867

    Google Scholar 

  6. Wang Q, Wang JJ, Boyce S, Fischer JE, Hasselgren PO (1998) Endotoxemia and IL-1β stimulate mucosal IL-6 production in different parts of the gastrointestinal tract. J Surg Res 76:27–31

    Article  PubMed  CAS  Google Scholar 

  7. Zhang H, Niesel DW, Peterson JW, Klimpel GR (1998) Lipoprotein release by bacteria: potential factor in bacterial pathogenesis. Infect Immun 66:5196–5201

    Google Scholar 

  8. Caradonna L, Amati L, Magrone T, Pellegrino WM, Jirillo E, Caccavo D (2000) Enteric bacteria lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J Endotoxin Res 6:205–214

    PubMed  CAS  Google Scholar 

  9. MacDermott RP (1999) Chemokines in the inflammatory bowel diseases. J Clin Immunol 19:266–272

    Article  PubMed  CAS  Google Scholar 

  10. Aoki KA (1978) Study of endotoxemia in ulcerative colitis and Crohn's disease. Acta Med Okoyama 32:147–158

    CAS  Google Scholar 

  11. Węglarz L, Dzierżewicz Z, Orchel A, Szczerba J, Jaworska-Kik M, Wilczok T (2003) Biological activity of Desulfovibrio desulfuricans lipopolysaccharides evaluated via interleukin-8 secretion by Caco-2 cells. Scand J Gastrenterol 38:73–79

    Google Scholar 

  12. Węglarz L, Dzierżewicz Z, Skop B, Orchel A, Parfiniewicz B, Wiśniowska B, Świątkowska L, Wilczok T (2003) Desulfovibrio desulfuricans lipopolysaccharides induce endothelial cell IL-6 and IL-8 secretion and E-selectin and VCAM-1 expression. Cell Mol Biol Lett 8:991–1003

    PubMed  Google Scholar 

  13. Dzierżewicz Z, Gawlik B, Cwalina B, Gonciarz K, Ziółkowski G, Gonciarz Z, Wilczok T (1994) Activity of sulphate-reducing bacteria in the human digestion tract. Bull Pol Acad Sci 42:171–176

    Google Scholar 

  14. Beerens H, Romond C (1977) Sulphate-reducing anaerobic bacteria in human feces. Am J Clin Nutr 30:1770–1776

    PubMed  CAS  Google Scholar 

  15. Goldstein EJC, Citron DM, Peraino VA, Cross SA (2003) Desulfovibrio desulfuricans bacteremia and review of human Desulfovibrio infections. J Clin Microbiol 41:2752–2754

    Article  Google Scholar 

  16. Tee W, Dyall-Smith M, Woods W, Eisen D (1996) Probable new species of Desulfovibrio isolated from a pyogenic liver abscess. J Clin Microbiol 34:1760–1764

    PubMed  CAS  Google Scholar 

  17. Rafter JJ (2002) Scientific basis of biomarkers and benefits of functional foods for reduction of disease risk: cancer. Br J Nutr 88 (Suppl 2):S219–S224

    Article  PubMed  CAS  Google Scholar 

  18. Orzechowski A, Ostaszewski P, Jank M, Berwid SJ (2002) Bioactive substances of plant origin in food-impact on genomics. Reprod Nutr Dev 42:461–477

    Article  PubMed  CAS  Google Scholar 

  19. Owen RW, Weisgerber UM, Spiegelhalder B, Bartsch H (1996) Faecal phytic acid and its relation to other putative markers of risk for colorectal cancer. Gut 38:591–597

    Article  PubMed  CAS  Google Scholar 

  20. Minihane AM, Rimbach G (2002) Iron absorption and the iron binding and anti-oxidant properties of phytic acid. Int J Food Sci Tech 37:741–748

    Article  CAS  Google Scholar 

  21. Shamsuddin AM, Vucenik I, Cole KE (1997) IP6: a novel anti-cancer agent. Life Sci 61:343–354

    Article  PubMed  CAS  Google Scholar 

  22. Ullah A, Shamsuddin AM (1990) Dose-dependent inhibition of large intestinal cancer by inositol hexaphosphate in F344 rats. Carcinogenesis 11:2219–2222

    Article  PubMed  CAS  Google Scholar 

  23. Jenab M, Thompson LU (1998) The influence of phytic acid in wheat bran on early biomarkers of colon carcinogenesis. Carcinogenesis 19:1087–1092

    Article  PubMed  CAS  Google Scholar 

  24. Graf E, Eaton JW (1990) Antioxidant function of phytic acid. Free Radical Biol Med 8:61–69

    Article  CAS  Google Scholar 

  25. Zhang Z, Song Y, Wang X-L (2005) Inositol hexaphosphate-induced enhancement of natural killer cell activity correlates with suppression of colon carcinogenesis in rats. World J Gastroenterol 11:5044–5046

    PubMed  CAS  Google Scholar 

  26. Eggleton P, Penhallow J, Crawford N (1991) Priming action of inositol hexakisphosphate (InsP6) on the stimulated respiratory burst in human neutrophils. Biochim Biophys Acta 1094:309–316

    Article  PubMed  CAS  Google Scholar 

  27. Dzierżewicz Z, Cwalina B, Gawlik B, Wilczok T, Gonciarz Z (1997) Isolation and evaluation of susceptibility to sulphasalazine of Desulfovibrio desulfuricans strains from the human digestive tract. Acta Microbiol Pol 46:175–187

    PubMed  Google Scholar 

  28. Postgate JR (1984) The sulphate-reducing bacteria. Cambridge University Press, Cambridge

    Google Scholar 

  29. Westphal O, Luderitz O, Bister FZ (1952) Bacterial strains and isolation of bacterial lipopolysaccharides. Naturforsch 78:148–154

    Google Scholar 

  30. Lawden KH, Pitts JM, Thomas JA, Lowe CR (1995) Rational computer-aided design of ligands that bind endotoxin. In: Levin J, Alving CR, Munford RS, Redl H (eds) Bacterial endotoxins: lipopolysaccharides from genes to therapy. Wiley-Liss, New York, pp 443–452

    Google Scholar 

  31. Schuerer-Maly C-C, Eckamnn L, Kagnoff MF, Falco MT, Maly F-E (1994) Colonic epithelial cell lines as a source of interleukin-8 stimulation by inflammatory cytokines and bacterial lipopolysaccharide. Immunology 81:85–91

    PubMed  CAS  Google Scholar 

  32. Fusunyan RD, Quinn JJ, Ohno Y, MacDermott RP, Sanderson IA (1998) Butyrate enhances interleukin (IL)-8 secretion by intestinal epithelial cells in response to IL-1β and lipopolysaccharide. Pediatr Res 43:84–90

    Article  PubMed  CAS  Google Scholar 

  33. Erickson KL (1986) Dietary fat modulation of immune response. Int J Immunopharmacol 8:529–543

    Article  PubMed  CAS  Google Scholar 

  34. Yoshida H, Miura S, Kishikawa H, Hirokawa M, Nakamizo H, Nakatsumi RC, Suzuki H, Saito H, Ishii H (2001) Fatty acids enhance GRO/CINC-1 and interleukin-6 production in rat intestinal epithelial cells. J Nutr 131:2943–2950

    PubMed  CAS  Google Scholar 

  35. Kjaer TMR, Frokier H (2002) Modulation of ovomucoid-specific oral tolerance in mice fed plant extracts containing lectins. Br J Nutr 88:671–680

    Article  PubMed  CAS  Google Scholar 

  36. Lavelle EC, Grant G, Pusztai A, Pfuller U, O’Hagan DT (2001) The identification of plant lectins with mucosal adjuwant activity. Immunology 102:77–86

    Article  PubMed  CAS  Google Scholar 

  37. Haas H, Falcone FH, Schramm G, Haisch K, Gibbs BF, Klaucke J, Poppelmann M, Becker WM, Gabius HJ, Schlaak M (1999) Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils. Eur J Immunol 29:918–927

    Article  PubMed  CAS  Google Scholar 

  38. Sandstrom B (2001) Micronutrient interactions: effect on absorption and bioavailability. Br J Nutr 85:S181–S185

    Article  PubMed  CAS  Google Scholar 

  39. Thurnham DI (2004) An overview of interactions between micronutrients and of micronutrients with drugs, genes and immune mechanisms. Nutr Res Rev 17:211–240

    Article  CAS  PubMed  Google Scholar 

  40. Wellinghausen N, Kirchner H, Rink L (1997) The immunobiology of zinc. Immunol Today 16:519–521

    Article  Google Scholar 

  41. Rink L, Gabriel P (2000) Zinc and the immune system. Proc Nutr Soc 59:541–552

    Article  PubMed  CAS  Google Scholar 

  42. Cui L, Takagi Y, Wasa M, Liboshi Y, Khan J, Nezu R, Okada A (1997) Induction of nitric oxide synthase in rat intestine by interleukin-1α may explain diarrhea associated with zinc deficiency. J Nutr 127:1729–1736

    PubMed  CAS  Google Scholar 

  43. Cui L, Takagi Y, Wasa M, Sando K, Khan J, Okada A (1999) Nitric oxide synthase inhibitor attenuates intestinal damage induced by zinc deficiency in rats. J Nutr 129:792–798

    PubMed  CAS  Google Scholar 

  44. Ligumsky M, Simon PL, Karmeli F, Rachmilewitz D (1990) Role of interleukin-1 in inflammatory bowel disease-enhanced production during active disease. Gut 31:686–689

    Article  PubMed  CAS  Google Scholar 

  45. Wang L, Walia B, Evans J, Gewirtz A, Merli D, Sitaraman SV (2003) IL-6 induces NF-κB activation in the intestinal epithelia. J Immunol 171:3194–3201

    PubMed  CAS  Google Scholar 

  46. McGee DW, Beagley KW, Aicher WK, McGhee JR (1993) Transforming growth factor-β and IL-1β act in synergy to enhance IL-6 secretion by the intestinal epithelial cell line, IEC-6. J Immunol 2:970–978

    Google Scholar 

  47. Hershko DD, Robb BW, Luo G, Hasselgren P-O (2002) Multiple transcription factors regulating the IL-6 gene are activated by cAMP in cultured Caco-2 cells. Am J Physiol Regul Integr Comp Physiol 283:R1140–R1148

    PubMed  Google Scholar 

  48. Wang Q, Sun X, Pritts TA, Wong HR, Hasselgren PO (2000) Induction of the stress response increases IL-6 production in intestinal mucosa of endotoxemic mice. Clin Sci 99:489–496

    Article  PubMed  CAS  Google Scholar 

  49. McGee DW, Beagley KW, Aicher WK, McGhee RM (1992) Transforming growth factor-β enhances interleukin-6 secretion by intestinal epithelial cells. Immunology 77:7–12

    PubMed  CAS  Google Scholar 

  50. Pritts TA, Hungness ES, Hershko DD, Robb BW, Sun X, Luo GJ, Fischer JE, Wong HR, Hasselgren PO (2002) Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cells. Am J Physiol Regul Integr Cop Physiol 282:R1016–R1026

    CAS  Google Scholar 

  51. Wilson M, Seymour R, Henderson B (1998) Bacterial perturbation of cytokine networks. Infect Immun 66:2401–2409

    PubMed  CAS  Google Scholar 

  52. Eggleton P (1999) Effect of IP6 on human neutrophil cytokine production and cell morphology. Anticancer Res 19:3711–3716.

    PubMed  CAS  Google Scholar 

  53. Cecconi O, Nelson RM, Roberts WG, Hanasaki K, Mannori G, Schultz C, Ulich TR, Aruffo A, Bevilaqua MP (1994) Inositol polyanions. Noncarbohydrate inhibitors of L- and P-selectin that block inflammation. J Biol Chem 269:15060–15066

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Medical University of Silesia, Narcyzów St. 1, 41–200, Sosnowiec, Poland

    Ludmiła Węglarz, Joanna Wawszczyk, Arkadiusz Orchel, Marzena Jaworska-Kik & Zofia Dzierżewicz

Authors
  1. Ludmiła Węglarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joanna Wawszczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arkadiusz Orchel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marzena Jaworska-Kik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zofia Dzierżewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ludmiła Węglarz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Węglarz, L., Wawszczyk, J., Orchel, A. et al. Phytic Acid Modulates In Vitro IL-8 and IL-6 Release from Colonic Epithelial Cells Stimulated with LPS and IL-1β. Dig Dis Sci 52, 93–102 (2007). https://doi.org/10.1007/s10620-006-9320-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9320-0

Keywords

Search

Navigation