Skip to main content

Anti-inflammatory effects of long-chain n-3 PUFA in rhinovirus-infected cultured airway epithelial cells

  • Ahmad Saedisomeolia (a1) (a2), Lisa G. Wood (a2) (a3) (a4), Manohar L. Garg (a1), Peter G. Gibson (a2) (a3) (a4) and Peter A. B. Wark (a2) (a3) (a4)...

Long-chain n-3 PUFA (LCn-3PUFA) including DHA and EPA, are known to decrease inflammation by inhibiting arachidonic acid (AA) metabolism to eicosanoids, decreasing the production of pro-inflammatory cytokines and reducing immune cell function. The aim of this study was to determine if EPA and DHA reduced the release of inflammatory mediators from airway epithelial cells infected with rhinovirus (RV). Airway epithelial cells (Calu-3) were incubated with EPA, DHA and AA for 24 h, followed by rhinovirus infection for 48 h. IL-6, IL-8 and interferon-γ-induced protein-10 (IP-10) released by cells were measured using ELISA. Viral replication was measured by serial titration assays. The fatty acid content of cells was analysed using GC. Cellular viability was determined by visual inspection of cells and lactate dehydrogenase release. DHA (400 μm) resulted in a significant 16 % reduction in IL-6 release after RV-43 infection, 29 % reduction in IL-6 release after RV-1B infection, 28 % reduction in IP-10 release after RV-43 infection and 23 % reduction in IP-10 release after RV-1B infection. Cellular DHA content negatively correlated with IL-6 and IP-10 release. None of the fatty acids significantly modified rhinovirus replication. DHA supplementation resulted in increased cellular content of DHA at the cost of AA, which may explain the decreased inflammatory response of cells. EPA and AA did not change the release of inflammatory biomarkers significantly. It is concluded that DHA has a potential role in suppressing RV-induced airway inflammation.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Anti-inflammatory effects of long-chain n-3 PUFA in rhinovirus-infected cultured airway epithelial cells
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Anti-inflammatory effects of long-chain n-3 PUFA in rhinovirus-infected cultured airway epithelial cells
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Anti-inflammatory effects of long-chain n-3 PUFA in rhinovirus-infected cultured airway epithelial cells
      Available formats
Corresponding author
*Corresponding author: Dr Lisa G. Wood, fax +61 2 49855850, email
Hide All
1Kromann N & Green A (1980) Epidemiological studies in the Upernavik district, Greenland. Incidence of some chronic diseases 1950–1974. Acta Med Scand 208, 401406.
2Dyerberg J & Bang HO (1979) Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 2, 433435.
3Martin RE (1998) Docosahexaenoic acid decreases phospholipase A2 activity in the neurites/nerve growth cones of PC12 cells. J Neurosci Res 54, 805813.
4Simopoulos AP (2002) Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 21, 495505.
5Tamura Y, Terano J, Saito A, et al. (1995) Enhancement of PGI2 formation by EPA in rat vascular smooth muscle cells. In Nutrition, Lipids, Health and Disease, p. 169 [Ong ASH, Niki E and Packer L, editors]. Champaign, IL: The American Oil Chemists' Society.
6Kang JX, Man SF, Brown NE, et al. (1992) Essential fatty acid metabolism in cultured human airway epithelial cells. Biochim Biophys Acta 1128, 267274.
7Harbige LS (2003) Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3. Lipids 38, 323341.
8Calder PC (2001) Polyunsaturated fatty acids, inflammation, and immunity. Lipids 36, 10071024.
9Glew R (1997) Lipid metabolism. In Textbook of Biochemistry, 4th ed., pp. 434 [Devlin T, editor]. New York: Wiley-Liss.
10Lee TH, Hoover RL, Williams JD, et al. (1985) Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 312, 12171224.
11Mann J & Skeaff M (1998) Lipids. In Essentials of Human Nutrition, p. 637 [Mann J and Truswell S, editors]. Oxford: Oxford University Press.
12Calder P (2001) ω-3 Polyunsaturated fatty acids, inflammation and immunity. In Fatty Acids and Lipids – New Findings, p. 109 [Hamazaki T and Okuyama H, editors]. Basel: Karger.
13Goldman DW, Pickett WC & Goetzl EJ (1983) Human neutrophil chemotactic and degranulating activities of leukotriene B5 (LTB5) derived from eicosapentaenoic acid. Biochem Biophys Res Commun 117, 282288.
14Jatakanon A, Uasuf C, Maziak W, et al. (1999) Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med 160, 15321539.
15Sun YC & Chu HW (2004) Do neutrophils actively participate in airway inflammation and remodeling in asthma? Chin Med J (Engl) 117, 17391742.
16Yasui K, Kobayashi N, Yamazaki T, et al. (2005) Neutrophilic inflammation in childhood bronchial asthma. Thorax 60, 704705.
17Browning LM, Krebs JD, Moore CS, et al. (2007) The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype. Diabetes Obes Metab 9, 7080.
18Bryan D, Forsyth K, Hart P, et al. (2006) Polyunsatuated fatty acids regulate cytokine and prostaglandin E2 production by respiratory cells in response to mast cell mediators. Lipids 41, 11011107.
19Abbate R, Gori AM, Martini F, et al. (1996) n-3 PUFA supplementation, monocyte PCA expression and interleukin-6 production. Prostaglandins Leukot Essent Fatty Acids 54, 439444.
20Bryan DL, Forsyth KD, Hart PH, et al. (2006) Polyunsaturated fatty acids regulate cytokine and prostaglandin E2 production by respiratory cells in response to mast cell mediators. Lipids 41, 11011107.
21Zeitlin L, Segev E, Fried A, et al. (2003) Effects of long-term administration of n-3 polyunsaturated fatty acids (PUFA) and selective estrogen receptor modulator (SERM) derivatives in ovariectomized (OVX) mice. J Cell Biochem 90, 347360.
22Fritsche KL, Anderson M & Feng C (2000) Consumption of eicosapentaenoic acid and docosahexaenoic acid impair murine interleukin-12 and interferon-gamma production in vivo. J Infect Dis 1821, Suppl. 1, S54S61.
23Skuladottir IH, Petursdottir DH & Hardardottir I (2007) The effects of omega-3 polyunsaturated fatty acids on TNF-alpha and IL-10 secretion by murine peritoneal cells in vitro. Lipids 42, 699706.
24Moon DO, Kim KC, Jin CY, et al. (2007) Inhibitory effects of eicosapentaenoic acid on lipopolysaccharide-induced activation in BV2 microglia. Int Immunopharmacol 7, 222229.
25Horia E & Watkins BA (2007) Complementary actions of docosahexaenoic acid and genistein on COX-2, PGE2 and invasiveness in MDA-MB-231 breast cancer cells. Carcinogenesis 28, 809815.
26Weldon SM, Mullen AC, Loscher CE, et al. (2007) Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J Nutr Biochem 18, 250258.
27Jia Y & Turek JJ (2005) Altered NF-kappaB gene expression and collagen formation induced by polyunsaturated fatty acids. J Nutr Biochem 16, 500506.
28Lo CJ, Chiu KC, Fu M, et al. (1999) Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res 82, 216221.
29Lee JY, Zhao L, Youn HS, et al. (2004) Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem 279, 1697116979.
30Lee JY, Sohn KH, Rhee SH, et al. (2001) Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 276, 1668316689.
31Barton GM & Medzhitov R (2003) Toll-like receptor signaling pathways. Science 300, 15241525.
32Blackwell TS & Christman JW (1997) The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol 17, 39.
33Zhu Z, Tang W, Ray A, et al. (1996) Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor kappa B-dependent transcriptional activation. J Clin Invest 97, 421430.
34Zhu Z, Tang W, Gwaltney JM Jr, et al. (1997) Rhinovirus stimulation of interleukin-8 in vivo and in vitro: role of NF-kappaB. Am J Physiol 273, L814L824.
35Calder P (1996) Immunomodulatory and anti-inflammatory effects of ω-3 polyunsaturated fatty acids. Proc Nutr Soc 55, 737774.
36Calder P (1998) Dietary fatty acids and lymphocyte functions. Proc Nutr Soc 57, 487502.
37Dreschers S, Dumitru CA, Adams C, et al. (2007) The cold case: are rhinoviruses perfectly adapted pathogens? Cell Mol Life Sci 64, 181191.
38Nicholson KG, Kent J & Ireland DC (1993) Respiratory viruses and exacerbations of asthma in adults. Br Med J 307, 982986.
39Johnston SL, Pattemore PK, Sanderson G, et al. (1995) Community study of role of viral infections in exacerbations of asthma in 9–11 year old children. Br Med J 310, 12251229.
40Grunberg K, Timmers MC, de Klerk EP, et al. (1999) Experimental rhinovirus 16 infection causes variable airway obstruction in subjects with atopic asthma. Am J Respir Crit Care Med 160, 13751380.
41Spurrell JC, Wiehler S, Zaheer RS, et al. (2005) Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection. Am J Physiol Lung Cell Mol Physiol 289, L85L95.
42Subauste MC, Jacoby DB, Richards SM, et al. (1995) Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure. J Clin Invest 96, 549557.
43Gern JE (2002) Rhinovirus respiratory infections and asthma. Am J Med 112, Suppl. 6A, 19S27S.
44Yamaya M & Sasaki H (2003) Rhinovirus and asthma. Viral Immunol 16, 99109.
45Calder PC (2001) Omega 3 polyunsaturated fatty acids, inflammation and immunity. World Rev Nutr Diet 88, 109116.
46Nair SS, Leitch J & Garg ML (1999) Specific modifications of phosphatidylinositol and nonesterified fatty acid fractions in cultured porcine cardiomyocytes supplemented with n-3 polyunsaturated fatty acids. Lipids 34, 697704.
47Reed L & Muench H (1938) A simple method of estimating fifty percent endpoints. Am J Hygiene 27, 493497.
48Karber G (1931) 50 % end-point calculation. Arch Exp Pathol Pharmak 162, 480483.
49Hatala MA, Rayburn J & Rose DP (1994) Comparison of linoleic acid and eicosapentaenoic acid incorporation into human breast cancer cells. Lipids 29, 831837.
50Croset M & Lagarde M (1986) In vitro incorporation and metabolism of icosapentaenoic and docosahexaenoic acids in human platelets – effect on aggregation. Thromb Haemost 56, 5762.
51Shahrzad S, Cadenas E, Sevanian A, et al. (2002) Impact of water-dispersible beadlets as a vehicle for the delivery of carotenoids to cultured cells. Biofactors 16, 8391.
52Sagar PS, Das UN, Koratkar R, et al. (1992) Cytotoxic action of cis-unsaturated fatty acids on human cervical carcinoma (HeLa) cells: relationship to free radicals and lipid peroxidation and its modulation by calmodulin antagonists. Cancer Lett 63, 189198.
53Kageyama K, Yamada R, Otani S, et al. (2000) Cytotoxicity of docosahexaenoic acid and eicosapentaenoic acid in tumor cells and the dependence on binding to serum proteins and incorporation into intracellular lipids. Oncol Rep 7, 7983.
54Chi TY, Chen GG & Lai PB (2004) Eicosapentaenoic acid induces Fas-mediated apoptosis through a p53-dependent pathway in hepatoma cells. Cancer J 10, 190200.
55Zalman LS, Brothers MA, Dragovich PS, et al. (2000) Inhibition of human rhinovirus-induced cytokine production by AG7088, a human rhinovirus 3C protease inhibitor. Antimicrob Agents Chemother 44, 12361241.
56Majumder S, Zhou LZ, Chaturvedi P, et al. (1998) p48/STAT-1alpha-containing complexes play a predominant role in induction of IFN-gamma-inducible protein, 10 kDa (IP-10) by IFN-gamma alone or in synergy with TNF-alpha. J Immunol 161, 47364744.
57Nazar AS, Cheng G, Shin HS, et al. (1997) Induction of IP-10 chemokine promoter by measles virus: comparison with interferon-gamma shows the use of the same response element but with differential DNA-protein binding profiles. J Neuroimmunol 77, 116127.
58Wu C, Ohmori Y, Bandyopadhyay S, et al. (1994) Interferon-stimulated response element and NF kappa B sites cooperate to regulate double-stranded RNA-induced transcription of the IP-10 gene. J Interferon Res 14, 357363.
59Korpi-Steiner NL, Bates ME, Lee WM, et al. (2006) Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation. J Leukoc Biol 80, 13641374.
60Mori TA & Beilin LJ (2004) Omega-3 fatty acids and inflammation. Curr Atheroscler Rep 6, 461467.
61Simopoulos AP (1991) Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 54, 438463.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 6
Total number of PDF views: 87 *
Loading metrics...

Abstract views

Total abstract views: 164 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 22nd November 2017. This data will be updated every 24 hours.