Mehmet Şükrü GÜLAY, Lokenga BADINGA, Alan EALY

CLA and EPA inhibit LPS-induced prostaglandin release from bovine endometrial cells through an NF-κB-dependent signaling mechanism

Although their action in antagonizing arachidonic acid metabolism is a key antiinflammatory effect of conjugated linoleic acid (CLA) and omega-3 polyunsaturated fatty acids (n-3 PUFA), these molecules have other antiinflammatory effects that might occur upstream of altered eicosanoid production. We examined the effects of two CLA isomers (c9,t11 and t10,c12 isomers), n-3 PUFA (EPA and DHA), and κNF-κB inhibitor (ammonium pyrrolidine dithiocarbamate (PDTC)) on lipopolysaccharide (LPS)-induced secretion of prostaglandins (PGE2 and PGF2a) by bovine endometrial (BEND) cells. LPS increased PGE2 and PGF2a concentrations in BEND cell-conditioned media in a concentration- and time-dependent manner. The c9,t11 CLA isomer and EPA decreased prostaglandinresponse to LPS. Addition of PDTC, alone or in combination with c9,t11 CLA or EPA, inhibited LPS-induced eicosanoid release into the culture medium. Results indicate that the c9,t11 CLA isomer and EPA inhibit the endometrial prostaglandin release in cattle and that these molecules may act through an NF-κB signaling mechanism.

PDF

___

1. Williams EJ, Fischer DP, Noakes DE, England GC, Rycroft A, Dobson H, Sheldon IM. The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow. Theriogenology 2007; 68: 549-559.
2. Herath S, Lilly ST, Fischer DP, Williams EJ, Dobson H, Bryant CE, Sheldon IM. Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2a to prostaglandin E2 in bovine endometrium. Endocrinology 2009; 150: 1912-1920.
3. Arosh JA, Banu SK, Kimmins S, Chapdelaine P, MacLaren LA, Fortier MA. Effect of interferon τ on prostaglandin biosynthesis, transport, and signaling at the time of maternal recognition of pregnancy in cattle: evidence of polycrine actions of prostaglandin E2. Endocrinology 2004; 145: 5280-5293.
4. Badinga L, Greene ES. Physiological properties of conjugated linoleic acid and implications for human health. Nutr Clin Pract 2006; 21: 367-373.
5. Rodriguez-Sallaberry C, Caldari-Torres C, Greene ES, Badinga L. Conjugated linoleic acid reduces phorbol ester-induced prostaglandin F2α production by bovine endometrial cells. J Dairy Sci 2006; 89: 3826-3832.
7. Mattos R, Staples CR, Arteche A, Wiltbank MC, Diaz FJ, Jenkins TC, Thatcher WW. The effects of feeding fish oil on uterine secretion of PGF2α, milk composition, and metabolic status of periparturient Holstein cows. J Dairy Sci 2004; 87: 921-932.
8. Petit HV, Germiquet C, Lebel D. Effect of feeding whole, unprocessed sunflower seeds and flaxseed on milk production, milk composition, and prostaglandin secretion in dairy cows. J Dairy Sci 2004; 87: 3889-3898.
9. Caldari-Torres C, Rodriguez-Sallaberry C, Greene ES, Badinga L. Differential effects of n-3 and n-6 fatty acids on prostaglandin F2a production by bovine endometrial cells. J Dairy Sci 2006; 89: 971-977.
10. Mattos R, Guzeloglu A, Badinga L, Staples CR, Thatcher WW. Polyunsaturated fatty acids and bovine interferon-τ modify phorbol ester-induced secretion of prostaglandin F2a and expression of prostaglandin endoperoxide synthase-2 and phospholipase-A2 in bovine endometrial cells. Biol Reprod 2003; 69: 780-787.
11. Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Brit J Clin Pharmacol 2013; 75: 645-662.
12. Liu SF, Ye X, Malik AB. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate prevents in vivo expression of proinflammatory genes. Circulation 1999; 100: 1330-1337.
13. Shemi D, Azab AN, Kaplanski J. Time-dependent effect of LPS on PGE2 and TNF-a production by rat glial brain culture: influence of COX and cytokine inhibitors. J Endotox Res 2001; 6: 877-881.
14. Kudo I, Murakami M. Prostaglandin E synthase, a terminal enzyme for prostaglandin E2 biosynthesis. Biochem J 2003; 375: 395-403.
15. Inada M, Matsumoto C, Uematsu S, Akira S, Miyaura C. Membrane-bound prostaglandin E synthase-1-mediated prostaglandin E2 production by osteoblasts plays a critical role in lipopolysaccharide-induced bone loss associated with inflammation. J Immunol 2006; 177: 1879-1885.
16. Diaz-Munoz MD, Osma-Garcia IC, Cacheiro-Llaguno C. Coordinated up-regulation of cyclooxygenase-2 and microsomal prostaglandin E synthase 1 transcription by nuclear factor kappa B and early growth response-1 in macrophages. Cell Signal 2010; 22: 1427-1436.
17. Matsumoto H, Naraba H, Murakami M, Kudo I, Yamaki K, Ueno A, Oh-Ishi S. Concordant induction of prostaglandin E2 synthase with cyclooxygenase-2 leads to preferred production of prostaglandin E2 over thromboxane and prostaglandin D2 in lipopolysaccharide-stimulated rat peritoneal macrophages. Biochem Biophys Res Commun 1997; 230: 110-114.
18. Murakami M, Naraba H, Tanioka T, Semmyo N, Nakatani Y, Kojima F, Ikeda T, Fueki M, Ueno A, Oh-Ishi S et al. Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 2000; 275: 32783-32792.
19. Tithof PK, Roberts MP, Guan W, Elgayyar M, Godkin JD. Distinct phospholipase A2 enzymes regulate prostaglandin E2 and F2α production in bovine endometrial cells. Reprod Biol Endocrinol 2007; 5: 16-27.
20. Godkin JD, Roberts MP, Elgayyar M, Guan W, Tithof PK. Phospholipase A2 regulation of bovine endometrial (BEND) cell prostaglandin production. Reprod Biol Endocrinol 2008; 6: 44-52.
21. Cheng WL, Lii CK, Chen HW, Lin TH, Liu KL. Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-κB pathway. J Agric Food Chem 2004; 52: 71-78.
22. Banni S, Angioni E, Casu V, Melis MP, Carta G, Gorongiu FP, Thompson H, Ip C. Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid. Carcinogenesis 1999; 20: 1019-1024.
23. Nugteren DH, Christ-Hazelhof E. Naturally occurring conjugated octadecatrienoic acids are strong inhibitors of prostaglandin biosynthesis. Prostaglandins 1987; 33: 403-417.
24. Iwakiri Y, Sampson DA, Allen KGD. Suppression of cyclooxygenase and inducible nitric oxide synthase expression by conjugated linoleic acid in murine macrophages. Prostaglandins Leukot Essent Fatty Acids 2002; 67: 435-443.
25. Peterson LD, Jeffery NM, Thies F, Sanderson P, Newsholme EA, Calder PC. Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity. Lipids 1998; 33: 171-180.
26. Healy DA, Wallace FA, Miles EA, Calder PC, Newsholme P. The effect of low to moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 2000; 35: 763-768.
27. Kew S, Mesa MD, Tricon S, Buckley R, Minihane AM, Yaqoob P. Effects of oils rich in eicopentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans. Am J Clin Nutr 2004; 79: 674-681.
28. Rees D, Miles EA, Banerjee T, Wells SJ, Roynette CE, Wahle KWJW, Calder PC. Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 2006; 83: 331-342.
29. Bousserouel S, Brouillet A, Bereziat G, Raymondjean M, Andreani M. Different effects of n-6 and n-3 polyunsaturated fatty acids on the activation of rat smooth muscle cells by interleukin-1b. J Lipid Res 2003; 44: 216-221.
30. Bulgarella JA, Patton D, Bull AW. Modulation of prostaglandin H synthase activity by conjugated linoleic acid (CLA) and specific CLA isomers. Lipids 2001; 36: 407-412.