Evaluation of pneumonitis and sialadenitis in Treg cell- and CCR2-Treg cell-transferred MRL/lpr mice

<p><b>Copyright information:</b></p><p>Taken from "Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4CD25regulatory T cells in MRL/lpr mice"</p><p>http://arthritis-research.com/content/9/1/R15</p><p>Arthritis Research & Therapy 2007;9(1):R15-R15.</p><p>Published online 7 Feb 2007</p><p>PMCID:PMC1860074.</p><p></p> The degrees of pneumonitis and sialadenitis of control and treated 17-week-old MRL/lpr mice were scored as described in Materials and methods. Values are presented as the mean and standard deviation (= 5 to 7 mice per group). Similar results were observed in two independent experiments. *< 0.01 versus control by Student's test. CCR2-Treg cell, CD4CD25Foxp3CCR2-transfected T cell; MRL/lpr, MRL/MpJ-/; Treg cell, CD4CD25Foxp3T cell

Comparison of pneumonitis and sialadenitis in Treg cell- and CCR2-Treg cell-transferred MRL/lpr mice

<p><b>Copyright information:</b></p><p>Taken from "Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4CD25regulatory T cells in MRL/lpr mice"</p><p>http://arthritis-research.com/content/9/1/R15</p><p>Arthritis Research & Therapy 2007;9(1):R15-R15.</p><p>Published online 7 Feb 2007</p><p>PMCID:PMC1860074.</p><p></p> Representative photographs are shown. Treg and CCR2-Treg cells were transferred via retro-orbital injection in 12-week-old MRL/lpr mice. One hundred thousand or 5 × 10cells were injected into mice twice every 2 weeks, and the pathological changes were evaluated 3 weeks after the last injection (that is, when the mice were 17 weeks old). Non-treated 17-week-old MRL/lpr mice were used as control. CCR2-Treg cell, CD4CD25Foxp3CCR2-transfected T cell; HE, hematoxylin and eosin; MRL/lpr, MRL/MpJ-/; Treg cell, CD4CD25Foxp3T cell

Monocyte chemoattractant protein-1 (MCP-1) expression in the lungs and submandibular glands of MRL/lpr mice

<p><b>Copyright information:</b></p><p>Taken from "Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4CD25regulatory T cells in MRL/lpr mice"</p><p>http://arthritis-research.com/content/9/1/R15</p><p>Arthritis Research & Therapy 2007;9(1):R15-R15.</p><p>Published online 7 Feb 2007</p><p>PMCID:PMC1860074.</p><p></p> Quantitative real-time polymerase chain reaction analysis was performed on total RNA prepared from lungs and submandibular glands of five mice at ages 8, 10, 12, 16, and 20 weeks during the development of pneumonitis and sialadenitis as described in Materials and methods. Results are calculated as a ratio of expression to the expression of . Representative immunohistochemistry results are shown. Formalin-fixed sections were deparaffinized and incubated with biotin-labeled goat anti-mouse MCP-1 polyclonal antibody, and the expression of MCP-1 was detected with avidin-biotin-peroxidase. The sections were counterstained with hematoxylin. MRL/lpr, MRL/MpJ-/

Kinetics of expression in the tissues after transfer of Treg and CCR2-Treg cells

<p><b>Copyright information:</b></p><p>Taken from "Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4CD25regulatory T cells in MRL/lpr mice"</p><p>http://arthritis-research.com/content/9/1/R15</p><p>Arthritis Research & Therapy 2007;9(1):R15-R15.</p><p>Published online 7 Feb 2007</p><p>PMCID:PMC1860074.</p><p></p> Five hundred thousand Treg or CCR2-Treg cells were injected into the retro-orbital vein of 14-week-old MRL/lpr mice. Then, the lungs and submandibular glands were harvested at 3 hours, 24 hours, 72 hours, 5 days, and 7 days after transfer. Quantitative real-time polymerase chain reaction analysis was performed on total RNA prepared from the above tissues. Results are calculated as a ratio of expression to the expression of . Analysis of the mononuclear cells in the lungs and submandibular glands of MRL/lpr mice after transfer of Treg and CCR2-Treg cells. The mononuclear cells in the lungs and submandibular glands were harvested at 3 hours and 24 hours after transfer as described in Materials and methods and analyzed by immunofluorescence on an Olympus IX70 inverted microscope. CCR2-Treg cells contain green fluorescent protein and red fluorescent protein (DsRed), whereas Treg cells contain only DsRed. Results are shown as a percentage of staining cells (Treg or CCR2-Treg cells) (= 3 or 4 mice per group). CCR2-Treg cell, CD4CD25Foxp3CCR2-transfected T cell; Foxp3, forkhead box p3; MRL/lpr, MRL/MpJ-/; Treg cell, CD4CD25Foxp3T cell

Enantioselective Synthesis of (+)-Penostatin E

The first enantioselective total synthesis of penostatin E has been accomplished. Two highly efficient and diastereoselective reactions, a Hosomi–Sakurai allylation and an intramolecular Pauson–Khand reaction, were utilized for the construction of the basic carbon framework of the target molecule as the key steps. A late-stage introduction of the side chain and a successful base-promoted elimination reaction afforded an efficient synthetic route to (+)-penostatin E

Clinical characteristics of the study population.

<p>Clinical characteristics of the study population.</p

CONSORT flow diagram.

<p>CONSORT flow diagram.</p

Comparison of changes in %FMD before and after treatment in each group.

<p>Comparison of changes in %FMD before and after treatment in each group.</p

Structure-Based Development of a Protein–Protein Interaction Inhibitor Targeting Tumor Necrosis Factor Receptor-Associated Factor 6

The interactions between tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and TNF superfamily receptors (TNFRSFs) are promising targets for rheumatoid arthritis (RA) treatment. However, due to the challenging nature of protein–protein interactions (PPIs), a potent inhibitor that surpasses the affinity of the TRAF6–TNFRSF interactions has not been developed. We developed a small-molecule PPI inhibitor of TRAF6–TNFRSF interactions using NMR and in silico techniques. The most potent compound, TRI4, exhibited an affinity higher than those of TNFRSFs and competitively inhibited a TRAF6–TNFRSF interaction. Structural characterization of the TRAF6–TRI4 complex revealed that TRI4 supplants key interactions in the TRAF6–TNFRSF interfaces. In addition, some TRAF6–TRI4 interactions extend beyond the TRAF6–TNFRSF interfaces and increase the binding affinity. Our successful development of TRI4 provides a new opportunity for RA treatment and implications for structure-guided development of PPI inhibitors