Ringseis Robert, Schulz Nadja, Saal Daniela, Eder Klaus
Institut für Agrar-und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhalden-Strasse 26, D-06108 Halle, Saale, Germany.
J Nutr Biochem. 2008 Sep;19(9):594-603. doi: 10.1016/j.jnutbio.2007.08.003. Epub 2007 Dec 21.
Gene expression and activity of matrix-metalloproteinases (MMP)-2 and -9 in macrophages are reduced through peroxisome proliferator-activated receptor gamma (PPARgamma)-dependent inhibition of NF-kappaB. Since conjugated linoleic acids (CLAs) are PPARgamma ligands and known to inhibit NF-kappaB via PPARgamma, we studied whether CLA isomers are capable of reducing gene expression and gelatinolytic activity of MMP-2 and -9 in PMA-differentiated THP-1 macrophages, which has not yet been investigated. Incubation of PMA-differentiated THP-1 cells with either c9t11-CLA, t10c12-CLA or linoleic acid (LA), as a reference fatty acid, resulted in a significant incorporation of the respective fatty acids into total cell lipids relative to control cells (P<.05). Treatment of PMA-differentiated THP-1 cells with 10 and 20 micromol/L troglitazone but not with 10 or 100 micromol/L c9t11-CLA, t10c12-CLA or LA reduced relative mRNA concentrations and activity of MMP-2 and MMP-9 compared to control cells (P<.05). DNA-binding activity of NF-kappaB and PPARgamma and mRNA expression of the NF-kappaB target gene cPLA2 were not influenced by treatment with CLA. In contrast, treatment of PMA-differentiated THP-1 cells with troglitazone significantly increased transactivation of PPARgamma and decreased DNA-binding activity of NF-kappaB and relative mRNA concentration of cPLA2 relative to control cells (P<.05). In conclusion, the present study revealed that CLA isomers, in contrast to troglitazone, did not reduce gene expression and activity of MMP-2 and -9 in PMA-differentiated THP-1 macrophages, which is probably explained by the observation that CLA isomers neither activated PPARgamma nor reduced DNA-binding activity of NF-kappaB. This suggests that CLA isomers are ineffective in MMP-associated extracellular matrix degradation which is thought to contribute to the progression and rupture of advanced atherosclerotic plaques.
通过过氧化物酶体增殖物激活受体γ（PPARγ）依赖的核因子κB（NF-κB）抑制作用，巨噬细胞中基质金属蛋白酶（MMP）-2和-9的基因表达及活性降低。由于共轭亚油酸（CLA）是PPARγ配体，且已知其通过PPARγ抑制NF-κB，我们研究了CLA异构体是否能够降低佛波酯（PMA）分化的THP-1巨噬细胞中MMP-2和-9的基因表达及明胶酶活性，此前尚未对此进行过研究。将PMA分化的THP-1细胞分别与反式-9，顺式-11-CLA、反式-10，顺式-12-CLA或作为对照脂肪酸的亚油酸（LA）孵育，相对于对照细胞，各自脂肪酸显著掺入总细胞脂质中（P<0.05）。用10和20 μmol/L曲格列酮处理PMA分化的THP-1细胞，而非用10或100 μmol/L反式-9，顺式-11-CLA、反式-10，顺式-12-CLA或LA处理，与对照细胞相比，MMP-2和MMP-9的相对mRNA浓度及活性降低（P<0.05）。CLA处理对NF-κB和PPARγ的DNA结合活性以及NF-κB靶基因cPLA2的mRNA表达没有影响。相反，与对照细胞相比，用曲格列酮处理PMA分化的THP-1细胞显著增加了PPARγ的反式激活，降低了NF-κB的DNA结合活性以及cPLA2的相对mRNA浓度（P<0.05）。总之，本研究表明，与曲格列酮不同，CLA异构体不会降低PMA分化的THP-1巨噬细胞中MMP-2和-9的基因表达及活性，这可能是因为观察到CLA异构体既不激活PPARγ，也不降低NF-κB的DNA结合活性。这表明CLA异构体在与MMP相关的细胞外基质降解中无效，而细胞外基质降解被认为会促进晚期动脉粥样硬化斑块的进展和破裂。
