title: Direct Regulation of TLR5 Expression by Caveolin-1.
abstract: Toll-like receptor 5 (TLR5) is a specific receptor for microbial flagellin and is one of the most well-known receptors in the TLR family. We reported previously that TLR5 signaling is well maintained during aging and that caveolin-1 may be involved in TLR5 signaling in aged macrophages through direct interactions. Therefore, it is important to clarify whether caveolin-1/TLR5 interactions affect TLR5 expression during aging. To assess the effect of caveolin-1 on TLR5, we analyzed TLR5 expression in senescent fibroblasts and aged tissues expressing high levels of caveolin-1. As expected, TLR5 mRNA and protein expression was well maintained in senescent fibroblasts and aged tissues, whereas TLR4 mRNA and protein were diminished in those cells and tissues. To determine the mechanism of caveolin-1-dependent TLR5 expression, we examined TLR5 expression in caveolin-1 deficient mice. Interestingly, TLR5 mRNA and protein levels were decreased dramatically in tissues from caveolin-1 knockout mice. Moreover, overexpressed caveolin-1 in vitro enhanced TLR5 mRNA through the MAPK pathway and prolonged TLR5 protein half-life through direct interaction. These results suggest that caveolin-1 may play a crucial role in maintaining of TLR5 by regulating transcription systems and increasing protein half-life.
authors.affiliation: Department of Biochemistry, Chonnam National University Medical School, Gwangju 501-746, Korea.|Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, Hwasun 519-809, Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, Chonnam National University Medical School, Gwangju 501-746, Korea.|Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Kim Cuc Thi
authors.initials: KC
authors.lastname: Nguyen
authors.affiliation: Department of Integrated OMICS for Biomedical Science, Yonsei University, Seoul 120-749, Korea.|College of Pharmacy, Yonsei University, Incheon 406-840, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Han
authors.affiliation: Division of life Science, Korea Basic Science Institute, Daejeon 305-333, Korea.
authors.forename: Ik-Soon
authors.initials: IS
authors.lastname: Jang
authors.affiliation: Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.|Translational Center for Regenerative Medicine (TRM), University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Fabian
authors.affiliation: Department of Biochemistry, Chonnam National University Medical School, Gwangju 501-746, Korea.|Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, Korea.|Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-746, Korea.|Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, Hwasun 519-809, Korea.
authors.forename: Kyung A
authors.initials: KA
authors.lastname: Cho
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D051198:Toll-Like Receptor 5 / Q000235:genetics* / Q000378:metabolism
chemical_list: C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5
keywords: aging; caveolin-1; senescence; toll-like receptor 5