Interleukin-1 receptor antagonist mediates toll-like receptor 3-induced inhibition of trophoblast adhesion to endometrial cells in vitro

STUDY QUESTION Is interleukin-1 receptor antagonist (IL-1RA) involved in the toll-like receptor 3 (TLR 3)-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro? SUMMARY ANSWER IL-1RA mediates the TLR 3-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro. WHAT IS KNOWN ALREADY It is well documented that endometrial TLR 3 activation leads to impairment of trophoblast binding to endometrial cells in vitro. IL-1RA is known as an anti-implantation factor, as its injection significantly reduced implantation rates in mice by an effect on endometrial receptivity. STUDY DESIGN, SIZE, DURATION Poly I:C was used as a TLR3 specific ligand and endometrial cells were either treated or not with Poly I:C (treated versus control) in vitro. IL-1RA was applied to block IL-1 signal transduction. IL-1RA was knocked down by Accell Human IL1RN siRNA. Flagellin was used to stimulate TLR 5. SP600125 (JNK) was applied to inhibit the mitogen-activated protein kinases (MAPK) pathway. BAY11 -7082 was used to inhibit the nuclear factor-κB (NF-κB) pathway. The experiments were performed in three replicates on three separate days. PARTICIPANTS/MATERIALS, SETTING, METHODS An in vitro assay was developed using RL95-2 (an endometrial cell line) and JAr (a trophoblast cell line) cells. Initially, the production of IL-1RA in RL95-2 cells in response to TLR 3 activation was measured. To determine whether the TLR 3-induced inhibition of trophoblast binding was mediated through IL-1RA: (i) we evaluated the effect of IL-1RA on the attachment of trophoblast cells to endometrial cells; (ii) we knocked down TLR3-induced IL-1RA gene expression by IL-1RA Small interfering RNA (siRNA) and evaluated trophoblast attachment to endometrial cells. Finally, to clarify through which pathway TLR 3-induced inhibition of trophoblast binding occurs: (i) activation of NF-κB and MAPK was detected by transfecting the cells with secreted placental alkaline phosphatase reporter plasmids bearing promoter sequences for each transcription factor; (ii) the inhibitors for NF-κB and MAPK were used to block signaling; (iii) it was then investigated whether addition of these inhibitors could restore the TLR 3-induced impairment of trophoblast attachment to the endometrial cells. MAIN RESULTS AND THE ROLE OF CHANCE Our results showed that addition of polyinosinic:polycytidylic acid (Poly I:C) to RL95-2 cells significantly increased the production of IL-1RA (P < 0.05). Addition of human recombinant IL-1RA to RL95-2 cells remarkably decreased the adhesion rate of trophoblast cells to endometrial cells (P < 0.05). In addition, suppression of TLR3-induced IL-1RA gene expression in RL95-2 cells significantly restored trophoblast cells attachment to endometrial cells in the presence of Poly I:C (P < 0.05). Only TLR3 and not TLR5 induced MAPK activation (P < 0.05). TLR3 ligation did not affect NF-κB activation. Of NF-kB and MAPK inhibitors, only MAPK's inhibitor could achieve restoration of spheroid adhesion to endometrial cells (P < 0.05). LIMITATIONS, REASONS FOR CAUTION This study has been only done in vitro. Future in vivo studies will confirm our data. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study have a potential clinical application in introducing IL-1RA as one of the diagnostic infertility markers in the endometrium, which can affect the process of embryo adhesion at the time of implantation. Moreover, based on the novel data obtained in the current study, blocking and regulating the MAPK pathway by its inhibitors can be used as a new strategy to prevent and treat virus-induced infertility cases in ART techniques. STUDY FUNDING/COMPETING INTEREST This study was partially funded by a Marie Curie IIF-253948 grant to I.C. and was partially funded by the author's institutions. The authors have no conflict of interest to declare

The metallicity - redshift relations for emission-line SDSS galaxies: examination of the dependence on the star formation rate

We analyse the oxygen abundance and specific star formation rates (sSFR) variations with redshift in star-forming SDSS galaxies of different masses. We find that the maximum value of the sSFR, sSFRmax, decreases when the stellar mass, Ms, of a galaxy increases, and decreases with decreasing of redshift. The sSFRmax can exceed the time-averaged sSFR by about an order of magnitude for massive galaxies. The metallicity - redshift relations for subsamples of galaxies with sSFR = sSFRmax and with sSFR = 0.1sSFRmax coincide for massive (log(Ms/Mo) > 10.5, with stellar mass Ms in solar units) galaxies and differ for low-mass galaxies. This suggests that there is no correlation between oxygen abundance and sSFR in massive galaxies and that the oxygen abundance correlates with the sSFR in low-mass galaxies. We find evidence in favour of that the irregular galaxies show, on average, higher sSFR and lower oxygen abundances than the spiral galaxies of similar masses and that the mass - metallicity relation for spiral galaxies differs slightly from that for irregular galaxies. The fact that our sample of low-mass galaxies is the mixture of spiral and irregular galaxies can be responsible for the dependence of the metallicity - redshift relation on the sSFR observed for the low-mass SDSS galaxies. The mass - metallicity and luminosity - metallicity relations obtained for irregular SDSS galaxies agree with corresponding relations for nearby irregular galaxies with direct abundance determinations. We find that the aperture effect does not make a significant contribution to the redshift variation of oxygen abundances in SDSS galaxies.Comment: 14 pages, 7 figures, accepted for publication in the MNRA

Human Trophoblast Cells Modulate Endometrial Cells Nuclear Factor kappa B Response to Flagellin In Vitro

Background: Implantation is a complex process that requires a delicate cooperation between the immune and reproductive system. Any interference in the fine balance could result in embryo loss and infertility. We have recently shown that Toll-like receptor 5 activation results in a decrease of trophoblast cells binding to endometrial cells in an in vitro model of human implantation. However, little is known about the downstream signalling leading to the observed failure in implantation and the factors that modulate this immune response. Methods and Principal Findings: An in vitro model of embryo implantation was used to evaluate the effect of trophoblasts and flagellin on the activation of NF-kappa B in endometrial cells and whether TLR5-related in vitro implantation failure is signalled through NF-kappa B. We generated two different NF-kappa B reporting cell lines by transfecting either an immortalized endometrial epithelial cell line (hTERT-EECs) or a human endometrial carcinoma cell line (Ishikawa 3-H-12) with a plasmid containing the secreted alkaline phosphatase (SEAP) under the control of five NF-kappa B sites. The presence of trophoblast cells as well as flagellin increased NF-kappa B activity when compared to controls. The NF-kappa B activation induced by flagellin was further increased by the addition of trophoblast cells. Moreover, blocking NF-kappa B signalling with a specific inhibitor (BAY11-7082) was able to restore the binding ability of our trophoblast cell line to the endometrial monolayer. Conclusions: These are the first results showing a local effect of the trophoblasts on the innate immune response of the endometrial epithelium. Moreover, we show that implantation failure caused by intrauterine infections could be associated with abnormal levels of NF-kappa B activation. Further studies are needed to evaluate the target genes through which NF-kappa B activation after TLR5 stimulation lead to failure in implantation and the effect of the embryo on those genes. Understanding these pathways could help in the diagnosis and treatment of implantation failure cases

Quiet Sun magnetic fields from simultaneous inversions of visible and infrared spectropolarimetric observations

We study the quiet Sun magnetic fields using spectropolarimetric observations of the infrared and visible Fe I lines at 6301.5, 6302.5, 15648 and 15653 A. Magnetic field strengths and filling factors are inferred by the simultaneous fit of the observed Stokes profiles under the MISMA hypothesis. The observations cover an intra-network region at the solar disk center. We analyze 2280 Stokes profiles whose polarization signals are above noise in the two spectral ranges, which correspond to 40% of the field of view. Most of these profiles can be reproduced only with a model atmosphere including 3 magnetic components with very different field strengths, which indicates the co-existence of kG and sub-kG fields in our 1.5" resolution elements. We measure an unsigned magnetic flux density of 9.6 G considering the full field of view. Half of the pixels present magnetic fields with mixed polarities in the resolution element. The fraction of mixed polarities increases as the polarization weakens. We compute the probability density function of finding each magnetic field strength. It has a significant contribution of kG field strengths, which concentrates most of the observed magnetic flux and energy. This kG contribution has a preferred magnetic polarity, while the polarity of the weak fields is balanced.Comment: 16 pages and 14 figure

Metal-THINGS: The association and optical characterization of SNRs with HI holes in NGC 6946

NGC~6946, also known as the `Fireworks' galaxy, is an unusual galaxy that hosts a total of 225 supernova remnant (SNR) candidates, including 147 optically identified with high [SII]/Ha line ratios. In addition, this galaxy shows prominent HI holes, which were analyzed in previous studies. Indeed, the connection between SNRs and HI holes together with their physical implications in the surrounding gas is worth of attention. This paper explores the connection between the SNRs and the HI holes, including an analysis of their physical link to observational optical properties inside and around the rims of the holes, using new integral field unit (IFU) data from the Metal-THINGS survey. We present an analysis combining previously identified HI holes, SNRs candidates, and new integral field unit (IFU) data from Metal-THINGS of the spiral galaxy NGC 6946. We analyze the distributions of the oxygen abundance, star formation rate surface density, extinction, ionization, diffuse ionized gas, and the Baldwin-Phillips-Terlevich classification throughout the galaxy. By analyzing in detail the optical properties of the 121 previously identify HI holes in NGC 6946, we find that the SNRs are concentrated at the rims of the HI holes. Furthermore, our IFU data shows that the star formation rate and extinction are enhanced at the rims of the holes. To a lesser degree, the oxygen abundance and ionization parameter show hints of enhancement on the rims of the holes. Altogether, this provides evidence of induced star formation taking place at the rims of the holes, whose origin can be explained by the expansion of superbubbles created by multiple supernova explosions in large stellar clusters dozens of Myr ago.Comment: Accepted by A&

Galaxy And Mass Assembly (GAMA) : galaxy close pairs, mergers and the future fate of stellar mass

ASGR acknowledges STFC and SUPA funding that were used to do this work. GAMA is funded by the STFC (UK), the ARC (Australia), the AAO and the participating institutions.We use a highly complete subset of the Galaxy And Mass Assembly II (GAMA-II) redshift sample to fully describe the stellar mass dependence of close pairs and mergers between 10(8) and 10(12)M(circle dot). Using the analytic form of this fit we investigate the total stellar mass accreting on to more massive galaxies across all mass ratios. Depending on how conservatively we select our robust merging systems, the fraction of mass merging on to more massive companions is 2.0-5.6 per cent. Using the GAMA-II data we see no significant evidence for a change in the close pair fraction between redshift z = 0.05 and 0.2. However, we find a systematically higher fraction of galaxies in similar mass close pairs compared to published results over a similar redshift baseline. Using a compendium of data and the function gamma(M) = A(1 + z)(m) to predict the major close pair fraction, we find fitting parameters of A = 0.021 +/- 0.001 and m = 1.53 +/- 0.08, which represents a higher low-redshift normalization and shallower power-law slope than recent literature values. We find that the relative importance of in situ star formation versus galaxy merging is inversely correlated, with star formation dominating the addition of stellar material below M* and merger accretion events dominating beyond M*. We find mergers have a measurable impact on the whole extent of the galaxy stellar mass function (GSMF), manifest as a deepening of the 'dip' in the GSMF over the next similar to Gyr and an increase in M* by as much as 0.01-0.05 dex.Publisher PDFPeer reviewe

The SAMI Galaxy Survey: the intrinsic shape of kinematically selected galaxies

Using the stellar kinematic maps and ancillary imaging data from the Sydney AAO Multi Integral field (SAMI) Galaxy Survey, the intrinsic shape of kinematically-selected samples of galaxies is inferred. We implement an efficient and optimised algorithm to fit the intrinsic shape of galaxies using an established method to simultaneously invert the distributions of apparent ellipticities and kinematic misalignments. The algorithm output compares favourably with previous studies of the intrinsic shape of galaxies based on imaging alone and our re-analysis of the ATLAS3D data. Our results indicate that most galaxies are oblate axisymmetric. We show empirically that the intrinsic shape of galaxies varies as a function of their rotational support as measured by the "spin" parameter proxy Lambda_Re. In particular, low spin systems have a higher occurrence of triaxiality, while high spin systems are more intrinsically flattened and axisymmetric. The intrinsic shape of galaxies is linked to their formation and merger histories. Galaxies with high spin values have intrinsic shapes consistent with dissipational minor mergers, while the intrinsic shape of low-spin systems is consistent with dissipationless multi-merger assembly histories. This range in assembly histories inferred from intrinsic shapes is broadly consistent with expectations from cosmological simulations.Comment: 15 pages, 11 figures, MNRAS in prin