Peroxisome-proliferator-activated receptor-gamma agonists inhibit the release of proinflammatory cytokines from RSV-infected epithelial cells.
The epithelial cells of the airways are the target cells for respiratory syncytial virus (RSV) infection and the site of the majority of the inflammation associated with the disease. Recently, peroxisome-proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor superfamily, has been shown to possess anti-inflammatory properties. Therefore, we investigated the role of PPARgamma agonists (15d-PGJ(2), ciglitazone and troglitazone) on the synthesis of RSV-induced cytokine release from RSV-infected human lung epithelial cells (A549). We observed that all PPARgamma ligands inhibited dose-dependently the release of TNF-alpha, GM-CSF, IL-1alpha, IL-6 and the chemokines CXCL8 (IL-8) and CCL5 (RANTES) from RSV-infected A549 cells. Concomitantly, the PPARgamma ligands diminished the cellular amount of mRNA encoding for IL-6, CXCL8 and CCL5 and the RSV-induced binding activity of the transcription factors NF-kappaB (p65/p50) and AP-1 (c-fos), respectively. Our data presented herein suggest a potential application of PPARgamma ligands in the anti-inflammatory treatment of RSV infection.
Arnold
Ralf
R
Institute of Medical Microbiology, Otto-von-Guericke-University, Leipzigerstr. 44, 39120 Magdeburg, Germany. ralf.arnold@medizin.uni-magdeburg.de
König
Wolfgang
W
D045744:Cell Line, Tumor; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000032:analysis; D002839:Chromans / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000821:virology*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D045162:Thiazolidinediones / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C477819:15-deoxyprostaglandin J2; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002839:Chromans; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000077288:Troglitazone; D015230:Prostaglandin D2; C039671:ciglitazone