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Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis
Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic dif...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721677/ https://www.ncbi.nlm.nih.gov/pubmed/31426355 http://dx.doi.org/10.3390/cells8080908 |
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author | Das, Manjusri Deb, Moonmoon Laha, Dipranjan Joseph, Matthew Kanji, Suman Aggarwal, Reeva Iwenofu, O. Hans Pompili, Vincent J. Jarjour, Wael Das, Hiranmoy |
author_facet | Das, Manjusri Deb, Moonmoon Laha, Dipranjan Joseph, Matthew Kanji, Suman Aggarwal, Reeva Iwenofu, O. Hans Pompili, Vincent J. Jarjour, Wael Das, Hiranmoy |
author_sort | Das, Manjusri |
collection | PubMed |
description | Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic differentiation, matrix metalloproteinases (MMPs), and inflammatory cytokines in K/BxN serum-induced mice. The severities of RA pathogenesis, as well as the causative and resultant cellular and molecular factors, were further confirmed in monocyte-specific KLF2 deficient mice. In addition, induction of RA resulted in a decreased level of KLF2 in monocytes isolated from both mice and humans along with higher migration of activated monocytes to the RA sites in humans. Mechanistically, overexpression of KLF2 decreased the level of MMP9; conversely, knockdown of KLF2 increased MMP9 in monocytes along with enrichment of active histone marks and histone acetyltransferases on the MMP9 promoter region. These findings define the critical regulatory role of myeloid KLF2 in RA pathogenesis. |
format | Online Article Text |
id | pubmed-6721677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67216772019-09-10 Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis Das, Manjusri Deb, Moonmoon Laha, Dipranjan Joseph, Matthew Kanji, Suman Aggarwal, Reeva Iwenofu, O. Hans Pompili, Vincent J. Jarjour, Wael Das, Hiranmoy Cells Article Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic differentiation, matrix metalloproteinases (MMPs), and inflammatory cytokines in K/BxN serum-induced mice. The severities of RA pathogenesis, as well as the causative and resultant cellular and molecular factors, were further confirmed in monocyte-specific KLF2 deficient mice. In addition, induction of RA resulted in a decreased level of KLF2 in monocytes isolated from both mice and humans along with higher migration of activated monocytes to the RA sites in humans. Mechanistically, overexpression of KLF2 decreased the level of MMP9; conversely, knockdown of KLF2 increased MMP9 in monocytes along with enrichment of active histone marks and histone acetyltransferases on the MMP9 promoter region. These findings define the critical regulatory role of myeloid KLF2 in RA pathogenesis. MDPI 2019-08-16 /pmc/articles/PMC6721677/ /pubmed/31426355 http://dx.doi.org/10.3390/cells8080908 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Das, Manjusri Deb, Moonmoon Laha, Dipranjan Joseph, Matthew Kanji, Suman Aggarwal, Reeva Iwenofu, O. Hans Pompili, Vincent J. Jarjour, Wael Das, Hiranmoy Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis |
title | Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis |
title_full | Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis |
title_fullStr | Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis |
title_full_unstemmed | Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis |
title_short | Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis |
title_sort | myeloid krüppel-like factor 2 critically regulates k/bxn serum-induced arthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721677/ https://www.ncbi.nlm.nih.gov/pubmed/31426355 http://dx.doi.org/10.3390/cells8080908 |
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