The Hα\alpha broadband photometric reverberation mapping of four Seyfert 1 galaxies

Broadband photometric reverberation mapping (PRM) have been investigated for AGNs in recent years, but mostly on accretion disk continuum RM. Due to the small fraction of broad emission lines in the broadband, PRM for emission lines is very challenging. Here we present an ICCF-Cut method for broadband PRM to obtain the H$\alpha$ broad line lag and apply it to four Seyfert 1 galaxies, MCG+08-11-011, NGC 2617, 3C 120 and NGC 5548. All of them have high quality broadband lightcurves with daily/sub-daily cadence, which enables us to extract H$\alpha$ lightcurves from the line band by subtracting the contributions from the continuum and host galaxy. Their extracted H$\alpha$ lightcurves are compared with the lagged continuum band lightcurves, as well as the lagged H$\beta$ lightcurves obtained by spectroscopic RM (SRM) at the same epochs. The consistency of these lightcurves and the comparison with the SRM H$\beta$ lags provide supports to the H$\alpha$ lags of these AGNs, in a range from 9 to 19 days, obtained by the ICCF-Cut, JAVELIN and $\chi^2$ methods. The simulations to evaluate the reliability of H$\alpha$ lags and the comparisons between SRM H$\beta$ and PRM H$\alpha$ lags indicate that the consistency of the ICCF-Cut, JAVELIN and $\chi^2$ results can ensure the reliability of the derived H$\alpha$ lags. These methods may be used to estimate the broad line region sizes and black hole masses of a large sample of AGNs in the large multi-epoch high cadence photometric surveys such as LSST in the future.Comment: 22 pages, 19 figures, accepted for publication in Ap

Evidence for an Outer Component in the Continuum Reverberation Mapping of Active Galactic Nuclei

Continuum reverberation mapping is widely used in studying the accretion disks of active galactic nuclei (AGNs). Some indirect evidence and simulations have indicated that the diffuse continuum, especially the strong Balmer continuum from the broad-line region, may contribute to the continuum in the u / U band. Here, we present direct evidence for this contribution. In this work, we apply the ICCF-Cut method to continuum reverberation mapping to extract the possible diffuse continuum light curves of six AGNs, using high-cadence, high-quality, and multiband observations. We find the existence of an outer component out of the accretion disk for each of the six AGNs in the Swift U band. Meanwhile, similar results can be derived with the JAVELIN Photometric Reverberation Mapping Model for four of them. The lags of the outer components are consistent with the predicted Balmer continuum lags, which are about half of the H β lag values. Our result directly reinforces the understanding that an outer component, especially the Balmer continuum in the rest-frame u / U band, can contribute significantly to the continuum reverberation lags of AGNs

Hα\alpha Time Delays of AGNs from the Zwicky Transcient Facility Broadband Photometry

In our previous work on broadband photometric reverberation mapping (PRM), we proposed the ICCF-Cut process to obtain the time lags of H$\alpha$ emission line from two broadband lightcurves via subtracting the continuum emission from the line band. Extending the work, we enlarge our sample to the Zwicky Transient Facility (ZTF) database. We adopt two criteria to select 123 type 1 AGNs with sufficient variability and smooth lightcurves from 3537 AGNs at $z<0.09$ with more than 100 epoch observations in the $g$ and $r$ bands from the ZTF database. We calculate the H$\alpha$ time lags for 23 of them which have previous spectroscopic reverberation mapping (SRM) results using ICCF-Cut, JAVELIN and $\chi ^2$ methods. Our obtained H$\alpha$ time lags are slightly larger than the H$\beta$ time lags, which is consistent with the previous SRM results and the theoretical model of the AGN broad line region. The comparisons between SRM and PRM lag distributions and between the subtracted emission line lightcurves indicate that after selecting AGNs with the two criteria, combining the ICCF-Cut, JAVELIN and $\chi^2$ methods provides an efficient way to get the reliable H$\alpha$ lags from the broadband PRM. Such techniques can be used to estimate the black hole masses of a large sample of AGNs in the large multi-epoch photometric sky surveys such as the Legacy Survey of Space and Time (LSST) and the survey from the Wide Field Survey Telescope (WFST) in the near future.Comment: 23 pages, 34 figures, accepted for publication in the Astrophysical Journa

Evidence for an Outer Component in the Continuum Reverberation Mapping of Active Galactic Nuclei

The continuum reverberation mapping is widely used in studying accretion disk of active galactic nuclei (AGN). While some indirect evidence and simulations indicated that the diffuse continuum, especially the strong Balmer continuum from the broad line region (BLR), may contribute to the continuum in the u/U band. Here, we present direct evidence for this contribution. In this work, we apply the ICCF-Cut method to continuum reverberation mapping to extract the possible diffuse continuum light curves of 6 AGNs with high cadence, high quality and multi-band observations. We find the existence of an outer component out of the accretion disk for each of 6 AGNs in the Swift U band. Meanwhile, similar results can be derived by JAVELIN Photometric Reverberation Mapping Model for 4 of them. The lags of the outer components are consistent with the predicted Balmer continuum lags, which are about half of the H$\beta$ lag values. Our result directly reinforces that an outer component, especially the Balmer continuum in the rest-frame u/U band, can contribute significantly to the continuum reverberation lags of AGNs.Comment: 17 pages, 10 figures, accepted for publication in the Astrophysical Journa

Macrophage Migration Inhibitory Factor Inhibits the Antiinflammatory Effects of Glucocorticoids via Glucocorticoid-Induced Leucine Zipper

Objective. Glucocorticoids remain a mainstay in the treatment of rheumatoid arthritis (RA). Dose-dependent adverse effects highlight the need for therapies that regulate glucocorticoid sensitivity to enable dosage reduction. Macrophage migration inhibitory factor (MIF) is a proinflammatory protein that has been implicated in the pathogenesis of RA; it impairs glucocorticoid sensitivity via MAPK phosphatase 1 (MKP-1) inhibition. The intracellular protein glucocorticoid-induced leucine zipper (GILZ) mimics the effects of glucocorticoids in models of RA, but whether it represents a target for the modulation of glucocorticoid sensitivity remains unknown. We undertook this study to investigate whether GILZ is involved in the regulation of glucocorticoid sensitivity by MIF. Methods. GILZ expression was studied in the presence and absence of MIF, and the role of GILZ in the MIF-dependent regulation of the glucocorticoid sensitivity mediator MKP-1 was studied at the level of expression and function. Results. GILZ expression was significantly inhibited by endogenous MIF, both basally and during responses to glucocorticoid treatment. The effects of MIF on GILZ were dependent on the expression and Akt-induced nuclear translocation of the transcription factor FoxO3A. GILZ was shown to regulate the expression of MKP-1 and consequent MAPK phosphorylation and cytokine release. Conclusion. MIF exerts its effects on MKP-1 expression and MAPK activity through inhibitory effects on GILZ. These findings suggest a previously unsuspected interaction between MIF and GILZ and identify GILZ as a potential target for the therapeutic regulation of glucocorticoid sensitivity

Divergent effects of endogenous and exogenous glucocorticoid-induced leucine zipper in animal models of inflammation and arthritis

Glucocorticoid-induced leucine zipper (GILZ) has effects on inflammatory pathways that suggest it to be a key inhibitory regulator of the immune system, and its expression is exquisitely sensitive to induction by glucocorticoids. We undertook this study to test our hypothesis that GILZ deficiency would exacerbate experimental immune-mediated inflammation and impair the effects of glucocorticoids on inflammation and, correspondingly, that exogenous GILZ would inhibit these events. GILZ(-/-) mice were generated using the Cre/loxP system, and responses were studied in delayed-type hypersensitivity (DTH), antigen-induced arthritis (AIA), K/BxN serum-transfer arthritis, and lipopolysaccharide (LPS)-induced cytokinemia. Therapeutic expression of GILZ via administration of recombinant adeno-associated virus expressing the GILZ gene (GILZ-rAAV) was compared to the effects of glucocorticoid in collagen-induced arthritis (CIA). Increased T cell proliferation and DTH were observed in GILZ(-/-) mice, but neither AIA nor K/BxN serum-transfer arthritis was affected, and GILZ deficiency did not affect LPS-induced cytokinemia. Deletion of GILZ did not impair the effects of exogenous glucocorticoids on CIA or cytokinemia. In contrast, overexpression of GILZ in joints significantly inhibited CIA, with an effect similar to that of dexamethasone. Despite effects on T cell activation, GILZ deficiency had no effect on effector pathways of arthritis and was unexpectedly redundant with effects of glucocorticoids. These findings do not support the hypothesis that GILZ is central to the actions of glucocorticoids, but the efficacy of exogenous GILZ in CIA suggests that further evaluation of GILZ in inflammatory disease is require

Macrophage migration inhibitory factor is essential for osteoclastogenic mechanisms in vitro and in vivo mouse model of arthritis

Macrophage migration inhibitory factor (MIF) enhances activation of leukocytes, endothelial cells and fibroblast-like synoviocytes (FLS), thereby contributing to the pathogenesis of rheumatoid arthritis (RA). A MIF promoter polymorphism in RA patients resulted in higher serum MIF concentration and worsens bone erosion; controversially current literature reported an inhibitory role of MIF in osteoclast formation. The controversial suggested that the prease role of MIF and its putative receptor CD74 in osteoclastogenesis and RA bone erosion, mediated by locally formed osteoclasts in response to receptor activator of NF-kappa B ligand (RANKL), is unclear. We reported that in an in vivo K/BxN serum transfer arthritis, reduced clinical and histological arthritis in MIF-/- and CD74(-/-) mice were accompanied by a virtual absence of osteoclasts at the synovium-bone interface and reduced osteoclast-related gene expression. Furthermore, in vitro osteoclast formation and osteoclast-related gene expression were significantly reduced in MIF-/- cells via decreasing RANKL-induced phosphorylation of NF-kappa B-p65 and ERK1/2. This was supported by a similar reduction of osteoclastogenesis observed in CD74(-/-) cells. Furthermore, a MIF blockade reduced RANKL-induced osteoclastogeriesis via deregulating RANKL-mediated NF-kappa B and NFATc1 transcription factor activation. These data indicate that MIF and CD74 facilitate RANKL-induced osteoclastogenesis, and suggest that MIF contributes directly to bone erosion, as well as inflammation, in RA. (C) 2014 Elsevier Ltd. All rights reserved