| NF-κB signaling participates in both RANKL- and IL-4-induced macrophage fusion: receptor cross-talk leads to alterations in NF-κB pathways. | |
| | |
MedLine Citation:
|
PMID: 21734075 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
NF-κB activation is essential for receptor activator for NF-κB ligand (RANKL)-induced osteoclast formation. IL-4 is known to inhibit the RANKL-induced osteoclast differentiation while at the same time promoting macrophage fusion to form multinucleated giant cells (MNG). Several groups have proposed that IL-4 inhibition of osteoclastogenesis is mediated by suppressing the RANKL-induced activation of NF-κB. However, we found that IL-4 did not block proximal, canonical NF-κB signaling. Instead, we found that IL-4 inhibited alternative NF-κB signaling and induced p105/50 expression. Interestingly, in nfκb1(-/-) bone marrow-derived macrophages (BMM), the formation of both multinucleated osteoclast and MNG induced by RANKL or IL-4, respectively, was impaired. This suggests that NF-κB signaling also plays an important role in IL-4-induced macrophage fusion. Indeed, we found that the RANKL-induced and IL-4-induced macrophage fusion were both inhibited by the NF-κB inhibitors IκB kinase 2 inhibitor and NF-κB essential modulator inhibitory peptide. Furthermore, overexpression of p50, p65, p52, and RelB individually in nfκb1(-/-) or nfκb1(+/+) BMM enhanced both giant osteoclast and MNG formation. Interestingly, knockdown of nfκb2 in wild-type BMM dramatically enhanced both osteoclast and MNG formation. In addition, both RANKL- and IL-4-induced macrophage fusion were impaired in NF-κB-inducing kinase(-/-) BMM. These results suggest IL-4 influences NF-κB pathways by increasing p105/p50 and suppressing RANKL-induced p52 translocation and that NF-κB pathways participate in both RANKL- and IL-4-induced giant cell formation. |
| | |
Authors:
|
Minjun Yu; Xiulan Qi; Jose L Moreno; Donna L Farber; Achsah D Keegan |
Related Documents
:
|
19031495 - Variability in the response of human dendritic cells stimulated with porphyromonas g... 9234775 - Activation of the interleukin-1beta precursor by treponema denticola: a potential role ... 16498065 - Protective and destructive immunity in the periodontium: part 1--innate and humoral imm... 18973535 - Experimental periodontitis in mice selected for maximal or minimal inflammatory reactio... 10537015 - Photopheresis: clinical applications and mechanism of action. 16719765 - Interactions between airway epithelial cells and dendritic cells: implications for the ... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-07-06 |
Journal Detail:
|
Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 187 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2011 Aug |
Date Detail:
|
Created Date: 2011-08-03 Completed Date: 2011-09-29 Revised Date: 2011-11-02 |
Medline Journal Info:
|
Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
|
Languages: eng Pagination: 1797-806 Citation Subset: AIM; IM |
Affiliation:
|
Department of Microbiology and Immunology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Bone Marrow Cells / immunology* Cell Fusion Cells, Cultured Giant Cells / immunology* Interleukin-4 / genetics, immunology* Mice Mice, Knockout NF-kappa B / genetics, immunology* Osteoclasts / immunology* Protein-Serine-Threonine Kinases / genetics, immunology RANK Ligand / genetics, immunology* |
| Grant Support | |
ID/Acronym/Agency:
|
AI038985/AI/NIAID NIH HHS; AI059775/AI/NIAID NIH HHS; R01 AI038985-14/AI/NIAID NIH HHS; R01 AI038985-15/AI/NIAID NIH HHS; R01 AI038985-16/AI/NIAID NIH HHS; R01 AI059775-01A2/AI/NIAID NIH HHS; R01 AI059775-02/AI/NIAID NIH HHS; R01 AI059775-03/AI/NIAID NIH HHS; R01 AI059775-04/AI/NIAID NIH HHS; R01 AI059775-05/AI/NIAID NIH HHS; R01 AI059775-05S1/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/NF-kappa B; 0/RANK Ligand; 0/Tnfsf11 protein, mouse; 207137-56-2/Interleukin-4; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.25/NF-kappa B kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The Dual Function Cytokine IL-33 Interacts with the Transcription Factor NF-{kappa}B To Dampen NF-{k...
Next Document: CD31 is required on CD4+ T cells to promote T cell survival during Salmonella infection.