Regulation of matrixmetalloproteinase-3 and matrixmetalloproteinase-13 by SUMO-2/3 through the transcription factor NF-κB

OBJECTIVE: Based on previous data that have linked the small ubiquitin-like modifier-1 (SUMO-1) to the pathogenesis of rheumatoid arthritis (RA), we have investigated the expression of the highly homologous SUMO family members SUMO-2/3 in human RA and in the human tumour necrosis factor α transgenic (hTNFtg) mouse model of RA and studied their role in regulating disease specific matrixmetalloproteinases (MMPs). METHODS: Synovial tissue was obtained from RA and osteoarthritis (OA) patients and used for histological analyses as well as for the isolation of synovial fibroblasts (SFs). The expression of SUMO-2/3 in RA and OA patients as well as in hTNFtg and wild type mice was studied by PCR, western blot and immunostaining. SUMO-2/3 was knocked down using small interfering RNA in SFs, and TNF-α induced MMP production was determined by ELISA. Activation of nuclear factor-κB (NF-κB) was determined by a luciferase activity assay and a transcription factor assay in the presence of the NF-κB inhibitor BAY 11-7082. RESULTS: Expression of SUMO-2 and to a lesser extent of SUMO-3 was higher in RA tissues and RASFs compared with OA controls. Similarly, there was increased expression of SUMO-2 in the synovium and in SFs of hTNFtg mice compared with wild type animals. In vitro, the expression of SUMO-2 but not of SUMO-3 was induced by TNF-α. The knockdown of SUMO-2/3 significantly increased the TNF-α and interleukin (IL)-1β induced expression of MMP-3 and MMP-13, accompanied by increased NF-κB activity. Induction of MMP-3 and MMP-13 was inhibited by blockade of the NF-κB pathway. TNF-α and IL-1β mediated MMP-1 expression was not regulated by SUMO-2/3. CONCLUSIONS: Collectively, we show that despite their high homology, SUMO-2/3 are differentially regulated by TNF-α and selectively control TNF-α mediated MMP expression via the NF-κB pathway. Therefore, we hypothesise that SUMO-2 contributes to the specific activation of RASF

Observation of a new Ξb−\Xi_b^- resonance

International audienceFrom samples of pp collision data collected by the LHCb experiment at s=7, 8 and 13 TeV, corresponding to integrated luminosities of 1.0, 2.0 and 1.5  fb-1, respectively, a peak in both the Λb0K- and Ξb0π- invariant mass spectra is observed. In the quark model, radially and orbitally excited Ξb- resonances with quark content bds are expected. Referring to this peak as Ξb(6227)-, the mass and natural width are measured to be mΞb(6227)-=6226.9±2.0±0.3±0.2  MeV/c2 and ΓΞb(6227)-=18.1±5.4±1.8  MeV/c2, where the first uncertainty is statistical, the second is systematic, and the third, on mΞb(6227)-, is due to the knowledge of the Λb0 baryon mass. Relative production rates of the Ξb(6227)-→Λb0K- and Ξb(6227)-→Ξb0π- decays are also reported

Observation of Bs0→D‾∗0ϕB_s^0 \to \overline{D}^{*0} \phi and search for B0→D‾0ϕB^0 \to \overline{D}^0 \phi decays

International audienceThe first observation of the Bs0→D¯*0ϕ decay is reported, with a significance of more than seven standard deviations, from an analysis of pp collision data corresponding to an integrated luminosity of 3  fb-1, collected with the LHCb detector at center-of-mass energies of 7 and 8 TeV. The branching fraction is measured relative to that of the topologically similar decay B0→D¯0π+π- and is found to be B(Bs0→D¯*0ϕ)=(3.7±0.5±0.3±0.2)×10-5, where the first uncertainty is statistical, the second systematic, and the third from the branching fraction of the B0→D¯0π+π- decay. The fraction of longitudinal polarization in this decay is measured to be fL=(73±15±4)%. The most precise determination of the branching fraction for the Bs0→D¯0ϕ decay is also obtained, B(Bs0→D¯0ϕ)=(3.0±0.3±0.2±0.2)×10-5. An upper limit, B(B0→D¯0ϕ)<2.0 (2.3)×10-6 at 90% (95%) confidence level is set. A constraint on the ω-ϕ mixing angle δ is set at |δ|<5.2° (5.5°) at 90% (95%) confidence level

Observation of the decay Bs0→D‾0K+K−B_s^0 \to \overline{D}^0 K^+ K^-

International audienceThe first observation of the Bs0→D¯0K+K- decay is reported, together with the most precise branching fraction measurement of the mode B0→D¯0K+K-. The results are obtained from an analysis of pp collision data corresponding to an integrated luminosity of 3.0  fb-1. The data were collected with the LHCb detector at center-of-mass energies of 7 and 8 TeV. The branching fraction of the B0→D¯0K+K- decay is measured relative to that of the decay B0→D¯0π+π- to be B(B0→D¯0K+K-)B(B0→D¯0π+π-)=(6.9±0.4±0.3)%, where the first uncertainty is statistical and the second is systematic. The measured branching fraction of the Bs0→D¯0K+K- decay mode relative to that of the corresponding B0 decay is B(Bs0→D¯0K+K-)B(B0→D¯0K+K-)=(93.0±8.9±6.9)%. Using the known branching fraction of B0→D¯0π+π-, the values of B(B0→D¯0K+K-)=(6.1±0.4±0.3±0.3)×10-5 and B(Bs0→D¯0K+K-)=(5.7±0.5±0.4±0.5)×10-5 are obtained, where the third uncertainties arise from the branching fraction of the decay modes B0→D¯0π+π- and B0→D¯0K+K-, respectively

Observation of Bs0→Dˉ∗0ϕB_s^0 \to \bar{D}^{*0} \phi and search for B0→Dˉ0ϕB^0 \to \bar{D}^0 \phi decays

The first observation of the $B^0_s → \bar{D}^{*0}ϕ$ decay is reported, with a significance of more than seven standard deviations, from an analysis of pp collision data corresponding to an integrated luminosity of 3  fb$^{−1}$, collected with the LHCb detector at center-of-mass energies of 7 and 8 TeV. The branching fraction is measured relative to that of the topologically similar decay $B^0 → \bar{D}^0 π^+ π^−$ and is found to be $\mathcal{B}(B^0_s → \bar{D}^{*0}ϕ)=(3.7±0.5±0.3±0.2) × 10^{−5}$, where the first uncertainty is statistical, the second systematic, and the third from the branching fraction of the $B^0 → \bar{D}^0 π^+ π^−$ decay. The fraction of longitudinal polarization in this decay is measured to be $f_L = (73±15±4)\%$. The most precise determination of the branching fraction for the $B^0_s → \bar{D}^{0}ϕ$ decay is also obtained, $\mathcal{B}(B^0_s → \bar{D}^0 ϕ)=(3.0±0.3±0.2±0.2) × 10^{−5}$. An upper limit,$\mathcal{B}(B^0 → \bar{D}^0 ϕ) < 2.0 (2.3) × 10^{−6}$ at 90% (95%) confidence level is set. A constraint on the $ω−ϕ$ mixing angle $δ$ is set at $|δ| < 5.2°$ (5.5°) at 90% (95%) confidence level

Measurement of Angular and CP Asymmetries in D0→π+π−μ+μ−D^0\to\pi^+\pi^-\mu^+\mu^- and D0→K+K−μ+μ−D^0\to K^+K^-\mu^+\mu^- decays

International audienceThe first measurements of the forward-backward asymmetry of the dimuon pair (AFB), the triple-product asymmetry (A2ϕ), and the charge-parity-conjugation asymmetry (ACP), in D0→π+π-μ+μ- and D0→K+K-μ+μ- decays are reported. They are performed using data from proton-proton collisions collected with the LHCb experiment from 2011 to 2016, corresponding to a total integrated luminosity of 5  fb-1. The asymmetries are measured to be AFB(D0→π+π-μ+μ-)=(3.3±3.7±0.6)%, A2ϕ(D0→π+π-μ+μ-)=(-0.6±3.7±0.6)%, ACP(D0→π+π-μ+μ-)=(4.9±3.8±0.7)%, AFB(D0→K+K-μ+μ-)=(0±11±2)%, A2ϕ(D0→K+K-μ+μ-)=(9±11±1)%, ACP(D0→K+K-μ+μ-)=(0±11±2)%, where the first uncertainty is statistical and the second systematic. The asymmetries are also measured as a function of the dimuon invariant mass. The results are consistent with the standard model predictions