دورية أكاديمية

Basal and IL-1β enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKα and IKKβ NF-κB activating kinases.

التفاصيل البيبلوغرافية
العنوان: Basal and IL-1β enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKα and IKKβ NF-κB activating kinases.
المؤلفون: Olivotto E; Laboratorio RAMSES, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy., Minguzzi M; Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy., D'Adamo S; Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy., Astolfi A; Department of Translational Medicine, University of Ferrara, Ferrara, Italy., Santi S; Institute of Molecular Genetics 'Luigi Luca Cavalli-Sforza', Unit of Bologna, CNR, Bologna, Italy.; IRCCS, Istituto Ortopedico Rizzoli, Bologna, Italy., Uguccioni M; Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy., Marcu KB; Departments of Biochemistry and Cell Biology and Pathology, SUNY, Stony Brook, NY, USA., Borzì RM; Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. rosamaria.borzi@ior.it.
المصدر: Scientific reports [Sci Rep] 2021 Nov 04; Vol. 11 (1), pp. 21697. Date of Electronic Publication: 2021 Nov 04.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: I-kappa B Kinase/*metabolism , Interleukin-1beta/*metabolism , Monocytes/*metabolism, Cells, Cultured ; Chemokine CCL2/metabolism ; Chemokines/immunology ; Chemokines/metabolism ; Chemotaxis/physiology ; Chondrocytes/metabolism ; Female ; Humans ; I-kappa B Kinase/physiology ; Inflammation ; Interleukin-1beta/physiology ; Male ; Middle Aged ; NF-kappa B/metabolism ; Osteoarthritis/metabolism ; Phosphorylation ; Protein Serine-Threonine Kinases ; Signal Transduction/physiology ; Transcription Factor RelA
مستخلص: IKKα and IKKβ are essential kinases for activating NF-κB transcription factors that regulate cellular differentiation and inflammation. By virtue of their small size, chemokines support the crosstalk between cartilage and other joint compartments and contribute to immune cell chemotaxis in osteoarthritis (OA). Here we employed shRNA retroviruses to stably and efficiently ablate the expression of each IKK in primary OA chondrocytes to determine their individual contributions for monocyte chemotaxis in response to chondrocyte conditioned media. Both IKKα and IKKβ KDs blunted both the monocyte chemotactic potential and the protein levels of CCL2/MCP-1, the chemokine with the highest concentration and the strongest association with monocyte chemotaxis. These findings were mirrored by gene expression analysis indicating that the lowest levels of CCL2/MCP-1 and other monocyte-active chemokines were in IKKαKD cells under both basal and IL-1β stimulated conditions. We find that in their response to IL-1β stimulation IKKαKD primary OA chondrocytes have reduced levels of phosphorylated NFkappaB p65pSer536 and H3pSer10. Confocal microscopy analysis revealed co-localized p65 and H3pSer10 nuclear signals in agreement with our findings that IKKαKD effectively blunts their basal level and IL-1β dependent increases. Our results suggest that IKKα could be a novel OA disease target.
(© 2021. The Author(s).)
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معلومات مُعتمدة: FIRB Grant: RBAP10KCNS Ministero dell'Istruzione, dell'Università e della Ricerca, Italy; Fondi Cinque per Mille to the IRCCS Istituto Ortopedico Rizzoli Ministero della Salute, Italy
المشرفين على المادة: 0 (CCL2 protein, human)
0 (Chemokine CCL2)
0 (Chemokines)
0 (IL1B protein, human)
0 (Interleukin-1beta)
0 (NF-kappa B)
0 (RELA protein, human)
0 (Transcription Factor RelA)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (TBK1 protein, human)
EC 2.7.11.10 (I-kappa B Kinase)
تواريخ الأحداث: Date Created: 20211105 Date Completed: 20220125 Latest Revision: 20220125
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8568921
DOI: 10.1038/s41598-021-01063-2
PMID: 34737366
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-021-01063-2