Cis-9,trans-11-CLA exerts anti-inflammatory effects in human bronchial epithelial cells and eosinophils: comparison to trans-10,cis-12-CLA and to linoleic acid.
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.
Jaudszus
Anke
A
Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 24, D-07743 Jena, Germany.
Foerster
Martin
M
Kroegel
Claus
C
Wolf
Ingrid
I
Jahreis
Gerhard
G
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018826:CD13 Antigens / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D047150:Eosinophil Cationic Protein / Q000096:biosynthesis; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D037181:Lectins, C-Type; D019787:Linoleic Acid / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D000099192:CD69 Antigens
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018826:CD13 Antigens; D047150:Eosinophil Cationic Protein; D016209:Interleukin-8; D037181:Lectins, C-Type; D019787:Linoleic Acid; D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; D000099192:CD69 Antigens; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid; C479220:RNASE3 protein, human