Complex Regulation of Tartrate-resistant Acid Phosphatase (TRAP) Expression by Interleukin 4 (IL-4)

Yu, Ming-Chih; Moreno, José L.; Stains, Joseph P.; Keegan, Achsah

doi:10.1074/jbc.m109.001016

Cited by 27 publications

(16 citation statements)

References 57 publications

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“…Nfκb2 knockdown significantly enhanced TRAP expression in IL-4 and RANKL plus IL-4 treated BMM without affecting NFATc1 expression (Figure 6B). This is consistent with our previous findings that IL-4-induced TRAP expression is mediated by STAT6 and is unrelated to NFATc1(24,34). These results suggest that p100/p52 inhibits the expression of STAT6 dependent genes induced by IL-4.…”

Section: Resultssupporting

confidence: 93%

“…Our previous study indicated that IL-4 modestly enhanced TRAP expression in BMM through STAT6 binding to the TRAP promoter (24). Interestingly, we found that nfκb2 knockdown significantly enhanced IL-4-induced TRAP expression.…”

Section: Discussionmentioning

confidence: 99%

“…TRAP staining was performed as previously described (24). MNG were identified using crystal violet staining.…”

Section: Methodsmentioning

confidence: 99%

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NF-κB Signaling Participates in Both RANKL- and IL-4–Induced Macrophage Fusion: Receptor Cross-Talk Leads to Alterations in NF-κB Pathways

Moreno

et al. 2011

The Journal of Immunology

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NF-κB activation is essential for RANKL-induced osteoclast formation. IL-4 is known to inhibit the RANKL-induced osteoclast differentiation, while at the same time promote 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 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 IKK2 inhibitor, and NEMO 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 NIK−/− 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.

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Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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NF-κB Signaling Participates in Both RANKL- and IL-4–Induced Macrophage Fusion: Receptor Cross-Talk Leads to Alterations in NF-κB Pathways

Moreno

et al. 2011

The Journal of Immunology

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“…Nuclear pellets were solubilized in lysis buffer B (20mM HEPES/400mM NaCl/1mM EDTA/10% Glycerol/1mM DTT, 1μg/ml protease inhibitor cocktail) at 4°C, followed by isolation of the nuclear lysate by centrifugation. Nuclear and cytoplasmic lysates were resolved on 4–20%SDS gels, and immunoblotted with anti-actin, anti-T-bet and anti-p50/105 antibodies as described (18). …”

Section: Methodsmentioning

confidence: 99%

Transcriptional Control of Rapid Recall by Memory CD4 T Cells

Wei

Huang

et al. 2011

The Journal of Immunology

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Memory T cells are distinguished from naive T cells by their rapid production of effector cytokines, although mechanisms for this recall response remain undefined. Here, we investigated transcriptional mechanisms for rapid IFN-γ production by antigen-specific memory CD4 T cells. In naive CD4 T cells, IFN-γ production only occurred following sustained antigen activation and was associated with high expression of the T-bet transcription factor required for Th1 differentiation, and T-bet binding to the IFN-γ promoter as assessed by chromatin immunoprecipitation analysis (ChIP). By contrast, immediate IFN-γ production by antigen-stimulated memory CD4 T cells occurred in the absence of significant nuclear T-bet expression or T-bet engagement on the IFN-γ promoter. We identified rapid induction of NFκB transcriptional activity and increased engagement of NFκB on the IFN-γ promoter at rapid times following TCR stimulation of memory compared to naive CD4 T cells. Moreover, pharmacologic inhibition of NFκB activity or peptide-mediated inhibition of NFκB p50 translocation abrogated early memory T cell signaling and TCR-mediated effector function. Our results reveal a molecular mechanism for memory T cell recall through enhanced NFκB p50 activation and promoter engagement, with important implications for memory T cell modulation in vaccines, autoimmunity and transplantation.

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“…RNA was treated with DNAse I (Qiagen) and cDNA was synthesized utilizing the High Capacity cDNA Reverse Transcription kit (Applied Biosystems, Carlsbad, CA) as instructed by the manufacturer. We used the following primers: type 1 procollagen (COL1A1), F: 5′-ACGTCCTGGTGAAGTTGGTC-3′ and R: 5′-CAGGGAAGCCTCTTTCTCCT-3′ [29]; tissue non-specific alkaline phosphatase (TNAP), F: 5′-AAGGCTTCTTCTTGCTGGTG-3′ and R: 5′-GCCTTACCCTCATGATGTCC-3′ [30]; osteocalcin (OC), F: 5′-CGGGAGCAGTGTGAGCTTA-3′ and R: 5′-AGGCGGTCTTCAAGCCATACT-3′ [31]; tartrate-resistant acid phosphatase (TRAP), F: 5′-CCAATGCCAAAGAGATCGCC-3′ and R: 5′-TCTGTGCAGAGACGTTGCCAAG-3′ [32]; cathepsin K (CTSK), F: 5′-AAAGCAGTACAACGGCAAGG-3′ and R: 5′-GAGCTCACATCTTGGGGAAG-3′ [33]; and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), F: 5′-TGCGACTTCAACAGCAACTC-3′ and R: 5′-ATGTAGGCCATGAGGTCCAC-3′ [34]. Amplifications were carried out in a total volume of 50 μl for 25–35 cycles with denaturation at 94°C for 45 seconds, annealing at 56°C for 45 seconds, and amplification at 72°C for 1 minute.…”

Section: Methodsmentioning

confidence: 99%

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair

Reumann¹,

Strachna²,

Yagerman³

et al. 2011

Bone

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Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1−/− mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1−/− mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1−/− callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair.

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Complex Regulation of Tartrate-resistant Acid Phosphatase (TRAP) Expression by Interleukin 4 (IL-4)

Cited by 27 publications

References 57 publications

NF-κB Signaling Participates in Both RANKL- and IL-4–Induced Macrophage Fusion: Receptor Cross-Talk Leads to Alterations in NF-κB Pathways

NF-κB Signaling Participates in Both RANKL- and IL-4–Induced Macrophage Fusion: Receptor Cross-Talk Leads to Alterations in NF-κB Pathways

Transcriptional Control of Rapid Recall by Memory CD4 T Cells

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair

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