title: WNT/β-catenin pathway is modulated in asthma patients and LPS-stimulated RAW264.7 macrophage cell line.
abstract: In the present study, we investigated the possibility that the WNT/β-catenin pathway plays a role in inflammatory responses both in an human inflammatory condition and in an in vitro inflammation model. First, we analyzed gene expression patterns of the peripheral blood cells from asthma patients compared with those from normal subjects using microarray analyses. We found that intracellular signaling molecules of the WNT/β-catenin pathway were significantly changed in asthma patients compared with the levels in the controls. Next, we determined whether major components of the WNT/β-catenin pathway were involved in the lipopolysaccharide (LPS)-induced inflammatory response of the RAW264.7 macrophage cell line. Among the members of WNT/β-catenin pathway, the protein levels of low-density lipoprotein receptor-related protein (LRP) 6, dishevelled (DVL) 2, and AXIN1, which were measured using western blotting, did not significantly change in the presence of LPS. In contrast, the LPS induced a rapid phosphorylation of glycogen synthase kinase (GSK) 3β and accumulation of β-catenin protein. It was found that β-catenin plays a significant role in the LPS-induced inflammatory response through the performance of small interfering RNA (siRNA) transfection experiments. The mRNA level of IL-6 was significantly elevated in β-catenin siRNA-transfected cells compared with that in control siRNA-transfected cells after LPS treatment. Furthermore, nuclear factor-κB (NF-κB) activity was also significantly increased in β-catenin siRNA-transfected cells compared with the level seen in control siRNA-transfected cells. Taken together, these results suggest that β-catenin plays a role as a negative regulator, preventing the overproduction of inflammatory cytokines such as IL-6 in LPS-induced inflammatory responses.
authors.affiliation: Department of Microbiology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Haeyong
authors.initials: H
authors.lastname: Lee
authors.forename: Sungmin
authors.initials: S
authors.lastname: Bae
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Yoon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D060466:Axin Protein / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D000072261:Dishevelled Proteins; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000276:immunology / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D051153:Wnt Proteins / Q000276:immunology* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000276:immunology*; D051176:beta Catenin / Q000276:immunology* / Q000378:metabolism
chemical_list: C555451:AXIN1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C555452:Axin1 protein, mouse; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; C508600:IL6 protein, human; D015850:Interleukin-6; C555475:LRP6 protein, human; D008070:Lipopolysaccharides; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D016328:NF-kappa B; D010750:Phosphoproteins; D051153:Wnt Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3