LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages
Abstract Long noncoding RNAs (lncRNAs) are emerging as major regulators of a variety of cell signaling processes. Many lncRNAs are expressed in immune cells and appear to play critical roles in the regulation of immune response. Here, we have investigated the potential role of a well-known lncRNA, H...
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Nature Portfolio
2018-10-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-018-33722-2 |
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| author | Monira Obaid S. M. Nashir Udden Paromita Deb Nadine Shihabeddin Md. Hasan Zaki Subhrangsu S. Mandal |
| author_facet | Monira Obaid S. M. Nashir Udden Paromita Deb Nadine Shihabeddin Md. Hasan Zaki Subhrangsu S. Mandal |
| author_sort | Monira Obaid |
| collection | DOAJ |
| description | Abstract Long noncoding RNAs (lncRNAs) are emerging as major regulators of a variety of cell signaling processes. Many lncRNAs are expressed in immune cells and appear to play critical roles in the regulation of immune response. Here, we have investigated the potential role of a well-known lncRNA, HOTAIR, in inflammatory and immune response. Our studies demonstrate that HOTAIR expression is induced in immune cells (macrophages) upon treatment with lipopolysaccharide (LPS). Knockdown of HOTAIR reduces NF-κB-mediated inflammatory gene and cytokine expression in macrophages. Inhibition of NF-κB resulted in down-regulation of LPS-induced expression of HOTAIR as well as IL-6 and iNOS expression. We further demonstrated that HOTAIR regulates activation of NF-κB and its target genes (IL-6 and iNOS) expression via facilitating the degradation of IκBα. HOTAIR knockdown reduces the expression of NF-κB target gene expression via inhibiting the recruitment of NF-κB and associated cofactors at the target gene promoters. Taken together, our findings suggest that HOTAIR is a critical player in NF-κB activation in macrophages suggesting its potential functions in inflammatory and immune response. |
| first_indexed | 2024-12-13T16:49:30Z |
| format | Article |
| id | doaj.art-1f55d91dc3db457aaef4b4a662414db3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:49:30Z |
| publishDate | 2018-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1f55d91dc3db457aaef4b4a662414db32022-12-21T23:38:04ZengNature PortfolioScientific Reports2045-23222018-10-018111810.1038/s41598-018-33722-2LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophagesMonira Obaid0S. M. Nashir Udden1Paromita Deb2Nadine Shihabeddin3Md. Hasan Zaki4Subhrangsu S. Mandal5Department of Chemistry and Biochemistry, The University of Texas at ArlingtonDepartment of Pathology, The University of Texas Southwestern Medical CenterDepartment of Chemistry and Biochemistry, The University of Texas at ArlingtonDepartment of Chemistry and Biochemistry, The University of Texas at ArlingtonDepartment of Pathology, The University of Texas Southwestern Medical CenterDepartment of Chemistry and Biochemistry, The University of Texas at ArlingtonAbstract Long noncoding RNAs (lncRNAs) are emerging as major regulators of a variety of cell signaling processes. Many lncRNAs are expressed in immune cells and appear to play critical roles in the regulation of immune response. Here, we have investigated the potential role of a well-known lncRNA, HOTAIR, in inflammatory and immune response. Our studies demonstrate that HOTAIR expression is induced in immune cells (macrophages) upon treatment with lipopolysaccharide (LPS). Knockdown of HOTAIR reduces NF-κB-mediated inflammatory gene and cytokine expression in macrophages. Inhibition of NF-κB resulted in down-regulation of LPS-induced expression of HOTAIR as well as IL-6 and iNOS expression. We further demonstrated that HOTAIR regulates activation of NF-κB and its target genes (IL-6 and iNOS) expression via facilitating the degradation of IκBα. HOTAIR knockdown reduces the expression of NF-κB target gene expression via inhibiting the recruitment of NF-κB and associated cofactors at the target gene promoters. Taken together, our findings suggest that HOTAIR is a critical player in NF-κB activation in macrophages suggesting its potential functions in inflammatory and immune response.https://doi.org/10.1038/s41598-018-33722-2HOX Transcript Antisense Intergenic RNA (HOTAIR)lncRNAsHOTAIR ExpressionEnhancer Of Zeste Homolog 2 (EZH2)Nuclear Factor Of Activated T (NFAT) |
| spellingShingle | Monira Obaid S. M. Nashir Udden Paromita Deb Nadine Shihabeddin Md. Hasan Zaki Subhrangsu S. Mandal LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages Scientific Reports HOX Transcript Antisense Intergenic RNA (HOTAIR) lncRNAs HOTAIR Expression Enhancer Of Zeste Homolog 2 (EZH2) Nuclear Factor Of Activated T (NFAT) |
| title | LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages |
| title_full | LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages |
| title_fullStr | LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages |
| title_full_unstemmed | LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages |
| title_short | LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages |
| title_sort | lncrna hotair regulates lipopolysaccharide induced cytokine expression and inflammatory response in macrophages |
| topic | HOX Transcript Antisense Intergenic RNA (HOTAIR) lncRNAs HOTAIR Expression Enhancer Of Zeste Homolog 2 (EZH2) Nuclear Factor Of Activated T (NFAT) |
| url | https://doi.org/10.1038/s41598-018-33722-2 |
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