Modulation of prostaglandin H synthase activity by conjugated linoleic acid (CLA) and specific CLA isomers

Bulgarella, Jennifer A.; Patton, David; Bull, Arthur W.

doi:10.1007/s11745-001-0736-2

Cited by 50 publications

(22 citation statements)

References 32 publications

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“…These 20-C metabolites of CLA have been recovered from livers of rats fed CLA (36). A more recent report also demonstrates inhibition of COX by various isomers of CLA (7). If COX inhibition is the method by which CLA is acting, we hypothesize that one or more enzymes in the lipoxygenase pathway are also being inhibited because rather than potentiation of the LT release [which is typically seen when COX alone is inhibited (19)], we showed that these mediators are also downregulated in CLA-fed animals.…”

Section: Discussionmentioning

confidence: 89%

Decreased antigen-induced eicosanoid release in conjugated linoleic acid-fed guinea pigs

Whigham¹,

Higbee

Bjorling

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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E. Cook. Decreased antigen-induced eicosanoid release in conjugated linoleic acid-fed guinea pigs. Am J Physiol Regulatory Integrative Comp Physiol 282: R1104-R1112, 2002 10.1152/ ajpregu.00075.2001.-This study investigated the capacity of conjugated linoleic acids (CLA) to reduce ex vivo antigeninduced release of eicosanoids in a type I hypersensitivity model. Guinea pigs were fed a diet containing 0.25% safflower oil (control) or 0.25% CLA [43% trans (t)10, cis (c)12; 41% c9, t11/t9, c11 18:2] for 2 wk before and during sensitization to ovalbumin (OVA). Lungs, tracheas, and bladders were incubated in physiological saline solution (PSS) for 1 h (basal mediator release) and challenged with OVA (0.01 g/l PSS) for 1 h (mediator release in response to antigen). Eicosanoids were quantified by HPLC/tandem mass spectrometry or enzyme immunoassay. CLA feeding resulted in no change in basal release but decreased eicosanoid release from sensitized tissues in response to antigen challenge in the following manner: thromboxane B 2, 6-keto-prostaglandin (PG)F1␣, PGF 2␣, PGD2, PGE2 by 57-75% in lung, 45-65% in trachea, and 38-60% in bladder; and leukotriene C 4/D4/E4 by 87, 90, and 50% in lung, trachea, and bladder, respectively. These data indicate that feeding CLA reduces lipid-derived inflammatory mediators produced by this type I hypersensitivity model. type I hypersensitivity; lung; trachea; bladder A GROUP OF 18-C FATTY ACID isomers referred to as conjugated linoleic acids (CLA) has been shown to have many biological effects, including modulation of the immune system (9, 26, 37, 38). We previously showed that dietary CLA lowered prostaglandin (PG)E 2 and histamine release in response to antigen challenge (42) in a guinea pig model for type I (immediate) hypersensitivity, a standard model for studying asthma and allergies (12, 41). The mechanism by which CLA lower PGE 2 levels may be, at least in part, inhibition of cyclooxygenase (COX), the enzyme responsible for the initial steps in converting arachidonic acid into prostanoids [PG and thromboxanes (TX)] (2). CLA isomers are similar to linoleic acid (the precursor of arachidonic acid), except the double bonds are in a conjugated formation (i.e., a 1,3-diene, not methylene interrupted). This structural difference (a conjugated diene) in similar 20-C fatty acids has been shown to inhibit the enzymatic activity of COX in vitro as measured by PG production (28).For many years, prostanoids have been implicated in the pathogenesis of type I hypersensitivity disorders such as asthma. We hypothesized that feeding dietary CLA would decrease prostanoids and leukotrienes (LT) released in response to antigen challenge. A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was used to quantify the prostanoids released from sensitized guinea pig tissues exposed to antigen in tissue baths. Stable products of each of the five possible pathways downstream of COX were analyzed. LT were quantified using a combination of LC/MS/MS and enzyme immunoassay. Previous investigation...

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Section: Discussionmentioning

confidence: 89%

Decreased antigen-induced eicosanoid release in conjugated linoleic acid-fed guinea pigs

Whigham¹,

Higbee

Bjorling

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Although 10t,12c-CLA was shown to reduce COX-2 protein expression and PGE 2 release, the concentration to reduce protein expression was higher than that required to decrease PGE 2 release. CLA has been shown to be a direct inhibitor of COX-2 enzymatic activity (17,35; unpublished data) and to reduce arachidonic acid level in phospholipids through the inhibition of fatty acid elongase (36). Hence, 10t,12c-CLA-induced decreases in COX-2 product formation could be the results of 1) decreased COX-2 protein, 2) decreased substrate availability, and 3) decreased COX-2 activity.…”

Section: Discussionmentioning

confidence: 94%

10t,12c-conjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo

Barnes

Bütz

et al. 2005

Journal of Lipid Research

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Previous data demonstrated that conjugated linoleic acid (CLA) reduced eicosanoid release from select organs. We hypothesized that one active CLA isomer was responsible for the reduced prostaglandin release and that the mechanism was through the inhibition of inducible cyclooxygenase-2 (COX-2). Here, we examined the effects of 10t,12c-CLA and 9c,11t-CLA on COX-2 protein/mRNA expression, prostaglandin E 2 (PGE 2 ) production, and the mechanism by which CLA affects COX-2 expression and prostaglandin release. The COX-2 protein expression level was inhibited 80% by 10t, 12c-CLA and 26% by 9c,11t-CLA at 100 M in vitro. PGE 2 production was decreased from 5.39 to 1.12 ng/2 ؋ 10 6 cells by 10t,12c-CLA and from 5.7 to 4.5 ng/2 ؋ 10 6 cells by 9c,11t-CLA at 100 M. Mice fed 10t,12c-CLA but not 9c,11t-CLA were found to have a 34% decrease in COX-2 protein and a 43% reduction of PGE 2 release in the lung. 10t,12c-CLA reduced COX-2 mRNA expression level by 30% at 100 M in vitro and by 30% in mouse lung in vivo. Reduced COX-2 mRNA was attributable to an inhibition of the nuclear factor B (NF-B) pathway by 10t,12c-CLA. These data suggested that the inhibition of NF-B was one of the mechanisms for the reduced COX-2 expression and PGE 2 release by 10t,12c-

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“…The 9c,11t-isomer appears to be the most effective, followed by the 9c,11c-, the 10t,12c-, and finally the 9t,11t-isomers [10]). A related finding has been observed with the inducible cyclooxygenase (COX-2 of the PGHS-2 complex) of cultured murine RAW macrophages [51], where several CLA isomers (e.g.…”

Section: Synthesis Of Eicosanoidsmentioning

confidence: 88%

Conjugated linoleic acids: all the same or to everyone its own function?

Martin

Valeille

2002

Reprod. Nutr. Dev.

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Modulation of prostaglandin H synthase activity by conjugated linoleic acid (CLA) and specific CLA isomers

Cited by 50 publications

References 32 publications

Decreased antigen-induced eicosanoid release in conjugated linoleic acid-fed guinea pigs

Decreased antigen-induced eicosanoid release in conjugated linoleic acid-fed guinea pigs

10t,12c-conjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo

Conjugated linoleic acids: all the same or to everyone its own function?

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