Skip to main content
SpringerLink
Log in

Polyunsaturated fatty acids regulate cytokine and prostaglandin E2 production by respiratory cells in response to mast cell mediators

  • Articles
  • Published:
Lipids

Abstract

A protective association between breastfeeding and the development of bronchial asthma has been demonstrated. However, a mechanism remains unclear. FA present in human milk but rare in infant formula have been associated with marked immunological modulation as well as some indications of protection from asthma development. We examined the effect of in vitro manipulation of membrane phospholipid on the production of cytokines and prostaglandin (PG)E2 by respiratory epithelial cells (A549) in response to stimulation by mast cell mediators of allergic disease [histamine, tumor necrosis factor (TNF)-α, interleukin (IL)-4 and IL-5]. DHA and CLA significantly decreased the production of IL-8 in response to stimulation by TNF-α [2907±970 (DHA) and 6471±1203 (CLA) vs. 12,287±2309 (control) pg/ml; P≤0.05, mean±SEM], whereas both EPA and DHA reduced histamine-stimulated RANTES (regulation on activation, T cell-expressed and-secreted) production [2314±861 (EPA) and 877±326 (DHA) vs. 8526±1118 (control) pg/ml; P≤0.03]. PGE2 released in response to histamine was decreased by n−3 [1305±399 (α-linolenic acid), 406±73 (EPA), and 265±32 (DHA) vs. 9324±3672 (control) pg/mL; P≤0.05] and increased by n−6 [18,843±4439 (arachidonic acid) vs. 9324±3672 (control) pg/mL; P=0.02], with CLA producing a decrease of the same magnitude as DHA [553±126 (CLA) vs. 9324±3672 (control) pg/mL; P=0.03]. This study demonstrates the potential for immunological manipulation of the respiratory epithelium by FA in situ during allergic responses and suggests that further investigation into FA intervention in infants via human milk or supplemented infant formula, to prevent the development of allergic disease, may be worthwhile.

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

Similar content being viewed by others

Abbreviations

A549:

human transformed alveolar epithelial cell line

AA:

arachidonic acid

ALA:

α-linolenic acid

COX:

cyclooxygenase

EIA:

enzyme immunoassay

IL:

interleukin

LA:

linoleic acid

LCPUFA:

long-chain PUFA

OA:

oleic acid

PGE2 :

prostaglandin E2

RANTES:

regulation on activation, T cell-expressed and-secreted

Th:

T helper

TNF:

tumor necrosis factor

References

  1. Gdalevich M., Mimouni, D., David, M., and Mimouni, M. (2001) Breast-Feeding and the Onset of Atopic Dermatitis in Childhood: A Systematic Review and Meta-analysis of Prospective Studies, J. Am. Acad. Dermatol. 45, 520–527.

    Article  PubMed  CAS  Google Scholar 

  2. Gdalevich, M., Mimouni, D., and Mimouni, M. (2001) Breast-Feeding and the Risk of Bronchial Asthma in Childhood: A Systematic Review with Meta-analysis of Prospective Studies, J. Pediatr. 139, 261–266.

    Article  PubMed  CAS  Google Scholar 

  3. Jensen, R.G. (ed.) (1995) Handbook of Milk Composition, Academic Press, San Diego.

    Google Scholar 

  4. Calder, P.C. (2003) n−3 Polyunsaturated Fatty Acids and Inflammation: From Molecular Biology to the Clinic, Lipids 38, 343–352.

    Article  PubMed  CAS  Google Scholar 

  5. Prescott, S.L., and Calder, P.C. (2004) n−3 Polyunsaturated Fatty Acids and Allergic Disease, Curr. Opin. Clin. Nutr. Metab. Care 7, 123–129.

    Article  PubMed  CAS  Google Scholar 

  6. Thijs, C., Houwelingen, A., Poorterman, I., Mordant, A., and van den Brandt, P. (2000) Essential Fatty Acids in Breast Milk of Atopic Mothers: Comparison with Non-atopic Mothers, and Effect of Borage Oil Supplementation, Eur. J. Clin. Nutr. 54, 234–238.

    Article  PubMed  CAS  Google Scholar 

  7. Duchen, K. (2001) Are Human Milk Polyunsaturated Fatty Acids (PUFA) Related to Atopy in the Mother and Her Child? Allergy 56, 587–592.

    Article  PubMed  CAS  Google Scholar 

  8. Mosmann, T.R., and Coffman, R.L. (1989) TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties, Annu. Rev. Immunol. 7, 145–173.

    Article  PubMed  CAS  Google Scholar 

  9. Busse, W.W., Coffman, R.L., Gelfand, E.W., Kay, A.B., and Rosenwasser, L.J. (1995) Mechanisms of Persistent Airway Inflammation in Asthma. A Role for T Cells and T-Cell Products, Am. J. Respir. Crit. Care Med. 152, 388–393.

    PubMed  CAS  Google Scholar 

  10. Djukanovic, R., Wilson, J.W., Britten, K.M., Wilson, S.J., Walls, A.F., Roche, W.R., Howarth, P.H., and Holgate, S.T. (1990) Quantitation of Mast Cells and Eosinophils in the Bronchial Mucosa of Symptomatic Atopic Asthmatics and Healthy Control Subjects Using Immunohistochemistry, Am. Rev. Respir. Dis. 142, 863–871.

    PubMed  CAS  Google Scholar 

  11. Bryan, D-L., Hart, P., Forsyth, K., and Gibson, R.A. (2001) Incorporation of a-Linolenic Acid (ALA) and Linoleic Acid (LA) into Human Epithelial Cell Lines, Lipids 36, 713–717.

    Article  PubMed  CAS  Google Scholar 

  12. Bryan, D-L., Hart, P., Forsyth, K.D., and Gibson, R.A. (2005) Modulation of Respiratory Syncytial Virus Induced Prostaglandin E2 Production by n−3 LCPUFA in Human Respiratory Epithelium, Lipids 40, 1007–1011.

    Article  PubMed  CAS  Google Scholar 

  13. Broekhuyse, R.M. (1974) Improved Lipid Extraction of Erythrocytes, Clin. Chim. Acta 51, 341–343.

    Article  PubMed  CAS  Google Scholar 

  14. Torres, A.G., Ney, J.G., Meneses, F., and Trugo, N.M.F. (2006) Polyunsaturated Fatty Acids and Conjugated Linoleic Acid Isomers in Breast Milk Are Associated with Plasma Non-esterified and Erythrocyte Membrane Fatty Acid Composition in Lactating Women, Br. J. Nutr. 95, 517–524.

    Article  PubMed  CAS  Google Scholar 

  15. Christie, W.W., Dobson, G., and Gunstone, F.D. (1997) Isomers in Commercial Samples of Conjugated Linoleic Acid, Lipids 32, 1231.

    Article  PubMed  CAS  Google Scholar 

  16. Smith, W.L., Garavito, R.M., and DeWitt, D.L. (1996) Prostaglandin Endoperoxide H Synthases (cyclooxygenases)-1 and-2, J. Biol. Chem. 271, 33157–33160.

    Article  PubMed  CAS  Google Scholar 

  17. Tilley, S.L., Coffman, T.M., and Koller, B.H. (2001) Mixed Messages: Modulation of Inflammation and Immune Responses by Prostaglandins and Thromboxanes, J. Clin. Invest 108, 15–23.

    Article  PubMed  CAS  Google Scholar 

  18. Pechkovsky, D.V., Zissel, G., Ziegenhagen, M.W., Einhaus, M., Taube, C., Rabe, K.F., Magnussen, H., Papadopoulos, T., Schlaak, M., and Muller-Quernheim, J. (2000) Effect of Proinflammatory Cytokines on Interleukin-8 mRNA Expression and Protein Production by Isolated Human Alveolar Epithelial Cells Type II in Primary Culture, Eur. Cytokine Netw. 11, 618–625.

    PubMed  CAS  Google Scholar 

  19. Sauty, A., Dziejman, M., Taha, R.A., Iarossi, A.S., Neote, K., Garcia-Zepeda, E.A., Hamid, Q., and Luster, A.D. (1999) The T Cell-Specific CXC Chemokines IP-10, Mig, and I-TAC Are Expressed by Activated Human Bronchial Epithelial Cells, J. Immunol. 162, 3549–3558.

    PubMed  CAS  Google Scholar 

  20. Grimbaldeston, M.A., Metz, M., Yu, M., Tsai, M., and Galli, S.J. (2006) Effector and Potential Immunoregulatory Roles of Mast Cells in IgE-Associated Acquired Immune Responses, Curr. Opin. Immunol. 18, 751–760.

    Article  PubMed  CAS  Google Scholar 

  21. Tonnel, A.B., Gosset, P., Molet, S., Tillie-Leblond, I., Jeannin, P., and Joseph, M. (1996) Interactions Between Endothelial Cells and Effector Cells in Allergic Inflammation, Ann. NY Acad. Sci. 796, 9–20.

    Article  PubMed  CAS  Google Scholar 

  22. Kaplan, A.P. (2001) Chemokines, Chemokine Receptors and Allergy, Int. Arch. Allergy Immunol. 124, 423–431.

    Article  PubMed  CAS  Google Scholar 

  23. Conti, P., Pang, X., Boucher, W., Letourneau, R., Reale, M., Barbacane, R.C., Thibault, J., and Theoharides, T.C. (1997) Impact of Rantes and MCP-1 Chemokines on in vivo Basophilic Cell Recruitment in Rat Skin Injection Model and Their Role in Modifying the Protein and mRNA Levels for Histidine Decarboxylase, Blood 89, 4120–4127.

    PubMed  CAS  Google Scholar 

  24. Conti, P., Reale, M., Barbacane, R.C., Letourneau, R., and Theoharides, T.C. (1998) Intramuscular Injection of hrRANTES Causes Mast Cell Recruitment and Increased Transcription of Histidine Decarboxylase in Mice: Lack of Effects in Genetically Mast Cell-Deficient W/WV Mice, FASEB J. 12, 1693–1700.

    PubMed  CAS  Google Scholar 

  25. Bardy, A.H., Seppala, T., Lillsunde, P., Kataja, J.M., Koskela, P., Pikkarainen, J., and Hiilesmaa, V.K. (1993) Objectively Measured Tobacco Exposure During Pregnancy—Neonatal Effects and Relation to Maternal Smoking, Br. J. Obstet. Gynaecol. 100, 721–726.

    PubMed  CAS  Google Scholar 

  26. Parsons, H.G., O'Loughlin, E.V., Forbes, D., Cooper, D., and Gall, D.G. (1988) Supplemental Calories Improve Essential Fatty Acid Deficiency in Cystic Fibrosis Patients, Pediatr. Res. 24, 353–356.

    PubMed  CAS  Google Scholar 

  27. Sosenko, I.R., Innis, S.M., and Frank, L. (1989) Menhaden Fish Oil, n−3 Polyunsaturated Fatty Acids, and Protection of Newborn Rats from Oxygen Toxicity, Pediatr. Res. 25, 399–404.

    PubMed  CAS  Google Scholar 

  28. Rayon, J.I., Carver, J.D., Wyble, L.E., Wiener, D., Dickey, S.S., Benford, V.J., Chen, L.T., and Lim, D.V. (1997) The Fatty Acid Composition of Maternal Diet Affects Lung Prostaglandin E2 Levels and Survival from Group B Streptococcal Sepsis in Neonatal Rat Pups, J. Nutr. 127, 1989–1992.

    PubMed  CAS  Google Scholar 

  29. Yu, G., Duchen, K., and Bjorksten, B. (1998) Fatty Acid Composition in Colostrum and Mature Milk from Non-atopic and Atopic Mothers During the First 6 Months of Lactation, Acta Paediatr. 87, 729–736.

    Article  PubMed  CAS  Google Scholar 

  30. Duchen, K., Yu, G., and Bjorksten, B. (1999) Polyunsaturated Fatty Acids in Breast Milk in Relation to Atopy in the Mother and Her Child, Int. Arch. Allergy Immunol. 118, 321–323.

    Article  PubMed  CAS  Google Scholar 

  31. Kankaanpaa, P., Nurmela, K., Erkkila, A., Kalliomaki, M., Holmberg-Marttila, D., Salminen, S., and Isolauri, E. (2001) Polyunsaturated Fatty Acids in Maternal Diet, Breast Milk, and Serum Lipid Fatty Acids of Infants in Relation to Atopy, Allergy 56, 633–638.

    Article  PubMed  CAS  Google Scholar 

  32. Duchen, K., Yu, G., and Bjorksten, B. (1998) Atopic Sensitization During the First Year of Life in Relation to Long Chain Polyunsaturated Fatty Acid Levels in Human Milk, Pediatr. Res. 44, 478–484.

    PubMed  CAS  Google Scholar 

  33. Duchen, K., Casas, R., Fageras-Bottcher, M., Yu, G., and Bjorksten, B. (2000) Human Milk Polyunsaturated Long-Chain Fatty Acids and Secretory Immunoglobulin A Antibodies and Early Childhood Allergy, Pediatr. Allergy Immunol. 11, 29–39.

    Article  PubMed  CAS  Google Scholar 

  34. Wright, S., and Bolton, C. (1989) Breast Milk Fatty Acids in Mothers of Children with Atopic Eczema, Br. J. Nutr. 62, 693–697.

    Article  PubMed  CAS  Google Scholar 

  35. Businco, L., Ioppi, M., Morse, N.L., Nisini, R., and Wright, S. (1993) Breast Milk from Mothers of Children with Newly Developed Atopic Eczema Has Low Levels of Long Chain Polyunsaturated Fatty Acids, J. Allergy Clin. Immunol. 91, 1134–1139.

    Article  PubMed  CAS  Google Scholar 

  36. Hodge, L., Salome, C.M., Peat, J.K., Haby, M.M., Xuan, W., and Woolcock, A.J. (1996) Consumption of Fish Oil and Childhood Asthma Risk, Med. J. Aust. 164, 137–140.

    PubMed  CAS  Google Scholar 

  37. Arm, J.P., Horton, C.E., Spur, B.W., Mencia-Huerta, J.-M., and Lee, T.H. (1989) The Effects of Dietary Supplementation with Fish Oil Lipids on the Airways Response to Inhaled Allergen in Bronchial Asthma, Am. Rev. Respir. Dis. 139, 1395–1400.

    PubMed  CAS  Google Scholar 

  38. Kirsch, C.M., Payan, D.G., Wong, M.Y., Dohlman, J.G., Blake, V.A., Petri, M.A., Offenberger, J., Goetzl, E.J., and Gold, W.M. (1988) Effect of Eicosapentaenoic Acid in Asthma, Clin. Allergy 18, 177–187.

    Article  PubMed  CAS  Google Scholar 

  39. Thien, F.C.K., Mencia-Huerta, J.M., and Lee, T.K. (1993) Dietary Fish Oil Effects on Seasonal Hay Fever and Asthma in Pollen-Sensitive Subjects, Am. Rev. Respir. Dis. 147, 1138–1143.

    PubMed  CAS  Google Scholar 

  40. Dry, J., and Vincent, D. (1991) Effect of a Fish Oil Diet on Asthma—Results of a One-Year Double-Blind Study, Int. Arch. Allergy Appl. Immunol. 95, 156–157.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Paediatrics and Child Health, Flinders University, GPO Box 2100, 5000, Adelaide, South Australia, Australia

    Dani-Louise Bryan & Kevin D. Forsyth

  2. Department of Microbiology and Infectious Diseases, Flinders University, Adelaide, South Australia, Australia

    Prue H. Hart

  3. Department of Child Nutrition Research Centre, Child Health Research Institute, Adelaide, South Australia, Australia

    Robert A Gibson

Authors
  1. Dani-Louise Bryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin D. Forsyth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prue H. Hart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert A Gibson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dani-Louise Bryan.

About this article

Cite this article

Bryan, DL., Forsyth, K.D., Hart, P.H. et al. Polyunsaturated fatty acids regulate cytokine and prostaglandin E2 production by respiratory cells in response to mast cell mediators. Lipids 41, 1101–1107 (2006). https://doi.org/10.1007/s11745-006-5059-9

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-006-5059-9

Keywords

Search

Navigation