interleukin-8 and trans-10-cis-12-conjugated-linoleic-acid

Trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) can reportedly alter the immune responses of phagocytes; however, it is unknown whether t10c12-CLA has a direct effect on the chemotaxis of peripheral blood polymorphonuclear neutrophillic leukocytes (PMNs). Here, we examined the effect of t10c12-CLA on the chemotaxis of porcine PMNs. The chemotactic response of porcine naïve PMNs was increased by porcine recombinant (pr) interleukin (IL)-8. Treatment with t10c12-CLA increased the chemotactic activity of porcine PMNs to IL-8 compared to porcine naïve PMNs, and enhanced their total cellular F-actin level. This increased chemotactic activity of t10c12-CLA-treated porcine PMNs was inhibited by cytochalasin D, an F-actin polymerization inhibitor. These results suggest that t10c12-CLA directly upregulates the chemotaxis of porcine PMNs, and that this effect may be associated with increased actin polymerization.

Topics: Actins; Animals; Chemotaxis; Cytochalasin D; Interleukin-8; Linoleic Acids, Conjugated; Neutrophils; Polymerization; Swine

Interaction of eosinophils and bronchial epithelial cells plays a pivotal role in maintaining inflammatory airway disease. Since conjugated linoleic acids (CLA) are suggested to exert anti-inflammatory effects, one purpose of this study was to compare cis-9,trans-11-CLA and trans-10,cis-12-CLA with regard to their influence on the stimulus-induced activation of eosinophils. ECP (eosinophil cationic protein) released in co-culture of stimulated and CLA-treated eosinophils with stimulated bronchial epithelial cells (BEAS-2B) was measured and cis-9,trans-11-CLA was found to be most potent in inhibiting ECP formation. Further, expression of the activation markers CD69 and CD13 induced by various stimuli (TNF-alpha, IL-5, IL-3) was significantly reduced in the presence of cis-9,trans-11-CLA. Subsequently, various concentrations of cis-9,trans-11-CLA vs. linoleic acid (LA, cis-9,cis-12-octadecadienoic acid) were tested for the effect on proliferative response and release of the pro-inflammatory cytokine IL-8 in stimulated BEAS-2B. Addition of cis-9,trans-11-CLA attenuated cell growth and significantly reduced IL-8 production at mRNA and protein levels. In contrast, LA had a slight stimulating effect on proliferation and was less effective in reducing the cytokine release. It was demonstrated that the inhibitory effect of cis-9,trans-11-CLA on IL-8 production is mediated through activation of the nuclear receptor PPARgamma, since blocking the receptor with a selective antagonist (GW9662) restored the stimulus-induced enhancement in IL-8 mRNA expression and protein secretion. PPARgamma has previously been shown to be closely involved in the downregulation of inflammation during hyperresponsiveness related to pulmonary immune responses. Thus, targeting PPARgamma, cis-9,trans-11-CLA might be of therapeutic value in the focus of airway disease while ameliorating inflammatory processes by affecting epithelial and eosinophil functions.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Base Sequence; Bronchi; CD13 Antigens; Cell Line; Cell Proliferation; Eosinophil Cationic Protein; Eosinophils; Epithelial Cells; Humans; Interleukin-8; Lectins, C-Type; Linoleic Acid; Linoleic Acids, Conjugated; RNA, Messenger; Stereoisomerism