Induction of Hypergammaglobulinemia and Macrophage Activation by Silicone Gels and Oils in Female A.SW Mice

Naim, John O.; Satoh, Minoru; Buehner, Norene; Ippolito, K. M. L.; Yoshida, Hideo; Nusz, D.; Kurtelawicz, L.; Cramer, Stewart F.; Reeves, Westley H.

doi:10.1128/cdli.7.3.366-370.2000

Cited by 33 publications

(16 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mineral oil pristane induces an autoimmune syndrome similar to SLE when injected in healthy mice, accompanied by a B cell polyclonal activation and generalized increase of Ig levels in all subclasses (39,40). Two-month-old CADϩ/ϩ and CADϪ/Ϫ mice received a single i.p.…”

Section: Induction Of Sle-like Autoimmune Disease Promotes Comparablementioning

confidence: 99%

Lack of Chromatin and Nuclear Fragmentation In Vivo Impairs the Production of Lupus Anti-Nuclear Antibodies

Frisoni

McPhie

Kang

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Nuclear autoantigens in systemic lupus erythematosus are thought to derive primarily from apoptotic cells, yet there is no direct evidence that interfering with apoptosis impairs the generation of lupus autoantibodies. Here we use a mouse model that lacks the endonuclease caspase-activated DNase (CAD), resulting in an absence of chromatin and nuclear fragmentation during apoptotic cell death. We show that in this mouse, production and release into circulation of chromatin is impaired after exposure to several apoptotic triggers, but that the absence of CAD does not interfere with upstream steps of apoptosis or immune system function. Finally we show that in CAD-mutant mice, impaired lupus autoimmunity is skewed toward known cytoplasmic components, and autoimmunity toward membrane autoantigens is preserved, while autoimmunity toward chromatin and other lupus nuclear targets is severely impaired or absent. We also show, as control, that the induction of experimental autoimmune encephalomyelitis is not affected by the absence of CAD. Thus, our work in vivo strongly suggests that apoptotic molecular steps during cell death generate nuclear autoantigens to sustain the specific autoimmune response in systemic lupus erythematosus.

show abstract

Section: Induction Of Sle-like Autoimmune Disease Promotes Comparablementioning

confidence: 99%

Lack of Chromatin and Nuclear Fragmentation In Vivo Impairs the Production of Lupus Anti-Nuclear Antibodies

Frisoni

McPhie

Kang

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…(100 μg/ 50 μl/mouse). Serum collection and ELISA for KLH-specific Abs were performed as described (10).…”

Section: Immunizationsmentioning

confidence: 99%

Cutting Edge: K63-Linked Polyubiquitination of NEMO Modulates TLR Signaling and Inflammation In Vivo

Florence

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

AgRAg receptor To address this issue, we introduced a point mutation (Lys 392 →Arg 392 or K392R) into the mouse germline that specifically disrupts K63-linked ubiquitination of NEMO at Lys 392 while sparing other Ubc13 substrates (NEMO-KR mice). NEMO-KR mice develop normal numbers of lymphocytes with no apparent defect in AgR signaling. However, primary macrophages and dendritic cells (DCs) from NEMO-KR mice exhibit blunted cytokine responses to TLR agonists. Consistent with this, survival rates among NEMO-KR mice are improved relative to those of control animals when challenged with doses of LPS that elicit lethal endotoxic shock. Surprisingly, NF-κB and MAPK signaling are largely unaffected in NEMO-KR cells, suggesting that Ubc13 impinges on these pathways via a mechanism independent of NEMO ubiquitination. We conclude that K63-linked ubiquitination of NEMO at Lys-392 functions as a rheostat for TLR-dependent responses in innate immunity. DC Materials and Methods NEMO-KR miceThe NEMO-targeting vector contained a point mutation in the Lys 392 codon (AAG) that converted it to an Arg codon (CGG). NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript (Neo) cassette was inserted into a StuI site between exons 9 and 10. The short and long homology arms were generated from the NcoI-StuI fragment encompassing exon 9 (1.6 kb) and the StuI-KpnI fragment encompassing exon 10 (4.0 kb). Generation of NEMO-KR mice (Mouse Genome Informatics no.3775942; Ikbkg tm1dwb ) was performed as described (9). All experiments were conducted according to guidelines of the Animal Care and Use Committee at Vanderbilt University (Nashville, TN). ImmunizationsKeyhole limpet hemocyanin (KLH; Sigma-Aldrich) in CFA (Difco) was injected i.p. (100 μg/ 50 μl/mouse). Serum collection and ELISA for KLH-specific Abs were performed as described (10). Cell purificationSplenic B and T lymphocytes were purified using CD43-negative selection and pan-T cell isolation kits, respectively (Miltenyi Biotec). For macrophages, mice were injected i.p. with 3% thioglycolate (2 ml; Sigma-Aldrich). Four days postinjection, peritoneal exudate cells were collected and cultured overnight in complete RPMI 1640 medium. Adherent cells were used as peritoneal macrophages. Bone marrow DC (BMDC) and macrophages were generated as described (11,12). Cell-based assaysFor cytokine responses, macrophages or BMDC were treated with agonists for 24h(5 × 10 4 cells/well). Levels of TNF, IFN-γ, and IL-6 in supernatants were measured using a BD CBA6 kit (BD Biosciences). Mouse IL-12/p40 was detected by ELISA (BD OptEIA Set) following cellular stimulation with LPS (100 ng/ml) and IFN-γ (30 ng/ml). Biochemical analysesMacrophage lysates were prepared and probed on Western blots for NF-κB and MAPK signaling components as described (8). Results Generation of NEMO-KR miceTo assess the physiologic role of NEMO ubiquitination, we introduced a point mutation into the mouse germline that prevents Ub attachment to Lys 392 . The X-linked NEMO allele in embryonic stem (ES) cel...

show abstract

“…Despite various levels of reported clinical success, synthetic implants can fail unpredictably and with severe clinical consequences as exemplified by the reported negative sequelae of silicone breast implants such as leakage, foreign material reaction, capsular contraction, extrusion, and dislocation. [29][30][31] Tissue engineering approaches have been utilized toward adipose tissue regeneration. Preadipocytes are considered advantageous in comparison to mature adipocytes because preadipocytes can proliferate to a certain extent ex vivo.…”

Section: Introductionmentioning

confidence: 99%

Vascularized Adipose Tissue Grafts from Human Mesenchymal Stem Cells with Bioactive Cues and Microchannel Conduits

et al. 2007

View full text Add to dashboard Cite

show abstract

Induction of Hypergammaglobulinemia and Macrophage Activation by Silicone Gels and Oils in Female A.SW Mice

Cited by 33 publications

References 21 publications

Lack of Chromatin and Nuclear Fragmentation In Vivo Impairs the Production of Lupus Anti-Nuclear Antibodies

Lack of Chromatin and Nuclear Fragmentation In Vivo Impairs the Production of Lupus Anti-Nuclear Antibodies

Cutting Edge: K63-Linked Polyubiquitination of NEMO Modulates TLR Signaling and Inflammation In Vivo

Vascularized Adipose Tissue Grafts from Human Mesenchymal Stem Cells with Bioactive Cues and Microchannel Conduits

Contact Info

Product

Resources

About