title: Trans-10, cis-12 conjugated linoleic acid and the PPAR-γ agonist rosiglitazone attenuate lipopolysaccharide-induced TNF-α production by bovine immune cells.
abstract: Lipopolysaccharide (LPS) modulates innate immunity through alteration of cytokine production by immune cells. The objective of this study was to examine the effect of exogenous conjugated linoleic acid (CLA) and PPAR-γ agonist, rosiglitazone, on LPS-induced tumor necrosis factor α (TNF-α) production by cultured whole blood from prepubertal Holstein heifers (mean age, 5.5 mo). Compared with unstimulated cells, addition of LPS (10 μg/mL) to the culture medium increased (P<0.03) peripheral blood mononuclear cell proliferation≤2.5-fold. Coincubation with interferon γ (5 ng/mL) further stimulated (P<0.01) the lymphoproliferative response to LPS. Lipopolysaccharide increased (P<0.01) TNF-α concentration in cultured whole blood in a dose- and time-dependent manner. The greatest TNF-α stimulation occurred after 12 h of exposure to 1 μg/mL LPS. Coincubation with trans-10, cis-12 CLA isomer (100 μM) or rosiglitazone (10 μM), a PPAR-γ agonist, decreased (P<0.01) LPS-induced TNF-α production by 13% and 29%, respectively. Linoleic acid and cis-9, trans-11 CLA isomer had no detectable effects on LPS-induced TNF-α production in cultured bovine blood. The PPAR-γ agonist-induced TNF-α attenuation was reversed when blood was treated with both rosiglitazone and GW9662, a selective PPAR-γ antagonist. Addition of rosiglitazone to the culture medium tended to reduce nuclear factor-κ Bp65 concentration in nuclear and cytosolic extracts isolated from cultured peripheral blood mononuclear cells. Results show that LPS is a potent inducer of TNF-α production in bovine blood cells and that trans-10, cis-12 CLA and PPAR-γ agonists may attenuate the pro-inflammatory response induced by LPS in growing dairy heifers. Additional studies are needed to fully characterize the involvement of nuclear factor-κ B in LPS signaling in bovine blood cells.
authors.affiliation: Department of Animal Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Perdomo
authors.forename: J E
authors.initials: JE
authors.lastname: Santos
authors.forename: L
authors.initials: L
authors.lastname: Badinga
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D007004:Hypoglycemic Agents; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C496197:trans-10,cis-12-conjugated linoleic acid; D000077154:Rosiglitazone; D007371:Interferon-gamma