Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury.

Thomas, Karen C,Roberts, Jessica K,Deering-Rice, Cassandra E,Romero, Erin G,Dull, Randal O,Lee, Jeewoo,Yost, Garold S,Reilly, Christopher A American Physiological Society 2012 American journal of physiology. Lung cellular and Vol.302 No.1

<P>Endogenous agonists of transient receptor potential vanilloid-1 (TRPV1) (endovanilloids) are implicated as mediators of lung injury during inflammation. This study tested the hypothesis that endovanilloids produced following lipopolysaccharide (LPS) treatment activate TRPV1 and cause endoplasmic reticulum stress/GADD153 expression in lung cells, representing a mechanistic component of lung injury. The TRPV1 agonist nonivamide induced GADD153 expression and caused cytotoxicity in immortalized and primary human bronchial, bronchiolar/alveolar, and microvascular endothelial cells, proportional to TRPV1 mRNA expression. In CF-1 mice, Trpv1 mRNA was most abundant in the alveoli, and intratracheal nonivamide treatment promoted Gadd153 expression in the alveolar region. Treatment of CF-1 mice with LPS increased Gadd153 in the lung, lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, and lung wet-to-dry weight ratio. Cotreating mice with LPS and the TRPV1 antagonist LJO-328 reduced Gadd153 induction and LDH in BAL but did not inhibit increases in lung wet-to-dry ratio. In Trpv1(-/-) mice treated with LPS, Gadd153 induction and LDH in BAL were reduced relative to wild-type mice, and the wet-to-dry weight ratios of lungs from both wild-type and Trpv1(-/-) mice decreased. Organic extracts of blood collected from LPS-treated mice were more cytotoxic to TRPV1-overexpressing cells compared with BEAS-2B cells and extracts from control mice, however, most pure endovanilloids did not produce cytotoxicity in a characteristic TRPV1-dependent manner. Collectively, these data indicate a role for TRPV1, and endogenous TRPV1 agonists, in ER stress and cytotoxicity in lung cells but demonstrate that ER stress and cytotoxicity are not essential for pulmonary edema.</P>

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

Haidy El-Azzamy,Nandor Gabor Than,Andrea Balogh,Roberto Romero,Yi Xu,Christopher LaJeunesse,Olesya Plazyo,Zhonghui Xu,Theodore G. Price,Zhong Dong,Adi L. Tarca,Zoltan Papp,Sonia S. Hassan,Tinnakorn Ch 대한병리학회 2017 Journal of Pathology and Translational Medicine Vol.51 No.3

Background: The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process. Methods: Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples. Results: The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found. Conclusions: Our data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.

Clinical findings influencing time to menarche post gonadotropin-releasing hormone agonist therapy in central precocious puberty

Wu Vickie,Zhao Victoria,Issa Rula,Wilkes Meredith,Wallach Elizabeth,Rapaport Robert,Romero Christopher,Yau Mabel 대한소아내분비학회 2021 Annals of Pediatirc Endocrinology & Metabolism Vol.26 No.3

Purpose: This study aimed to evaluate the time interval to menarche after gonadotropin-releasing hormone agonist (GnRHa) treatment in females with central precocious puberty (CPP) and to identify factors contributing to timing of menarche.Methods: We retrospectively reviewed medical records of 39 females with CPP who reached menarche after GnRHa treatment (leuprolide or histrelin). CPP diagnostic criteria were breast development at <8 years old, measurable pubertal luteinizing hormone and/or estradiol concentrations, and bone age advancement. Indications to treat were advanced bone age and psychosocial concerns. Descriptive summaries were reported as frequency and proportion for categorical variables and mean and standard deviation for continuous measures. Linear regression models were developed to evaluate the associations of clinical factors with the time interval to menarche.Results: Mean age was 9.4±1.6 years at treatment onset, and treatment duration was 2.2±1.4 years. Menarche occurred at 12.6±1.1 years, which was 1.04±0.5 years after treatment discontinuation. This was negatively associated with Tanner stage of breast development and bone age at treatment onset and change in bone age during treatment. No association was seen between time interval to menarche and treatment duration, medication, or body mass index.Conclusion: We found the average time interval to menarche after GnRHa treatment in our population of female patients with CPP to be 1.04±0.5 years; this is in agreement with other reports. Tanner stage of breast development, bone age at treatment onset, and change in bone age were negatively associated with time interval to menarche. These data provide clinical correlates that assist providers during anticipatory guidance of patients with CPP after GnRHa treatment.

Transient receptor potential vanilloid-1 (TRPV1) is a mediator of lung toxicity for coal fly ash particulate material.

Deering-Rice, Cassandra E,Johansen, Mark E,Roberts, Jessica K,Thomas, Karen C,Romero, Erin G,Lee, Jeewoo,Yost, Garold S,Veranth, John M,Reilly, Christopher A American Society for Pharmacology and Experimental 2012 Molecular pharmacology Vol.81 No.3

<P>Environmental particulate matter (PM) pollutants adversely affect human health, but the molecular basis is poorly understood. The ion channel transient receptor potential vanilloid-1 (TRPV1) has been implicated as a sensor for environmental PM and a mediator of adverse events in the respiratory tract. The objectives of this study were to determine whether TRPV1 can distinguish chemically and physically unique PM that represents important sources of air pollution; to elucidate the molecular basis of TRPV1 activation by PM; and to ascertain the contributions of TRPV1 to human lung cell and mouse lung tissue responses exposed to an insoluble PM agonist, coal fly ash (CFA1). The major findings of this study are that TRPV1 is activated by some, but not all of the prototype PM materials evaluated, with rank-ordered responses of CFA1 > diesel exhaust PM > crystalline silica; TRP melastatin-8 is also robustly activated by CFA1, whereas other TRP channels expressed by airway sensory neurons and lung epithelial cells that may also be activated by CFA1, including TRPs ankyrin 1 (A1), canonical 4α (C4α), M2, V2, V3, and V4, were either slightly (TRPA1) or not activated by CFA1; activation of TRPV1 by CFA1 occurs via cell surface interactions between the solid components of CFA1 and specific amino acid residues of TRPV1 that are localized in the putative pore-loop region; and activation of TRPV1 by CFA1 is not exclusive in mouse lungs but represents a pathway by which CFA1 affects the expression of selected genes in lung epithelial cells and airway tissue.</P>

Gaia17biu/SN 2017egm in NGC 3191: The Closest Hydrogen-poor Superluminous Supernova to Date Is in a “Normal,” Massive, Metal-rich Spiral Galaxy

Bose, Subhash,Dong, Subo,Pastorello, A.,Filippenko, Alexei V.,Kochanek, C. S.,Mauerhan, Jon,Romero-Cañ,izales, C.,Brink, Thomas G.,Chen, Ping,Prieto, J. L.,Post, R.,Ashall, Christopher,Grupe, Di American Astronomical Society 2018 The Astrophysical journal Vol.853 No.1

<P>Hydrogen-poor superluminous supernovae (SLSNe-I) have been predominantly found in low-metallicity, star-forming dwarf galaxies. Here we identify Gaia17biu/SN 2017egm as an SLSN-I occurring in a 'normal' spiral galaxy (NGC 3191) in terms of stellar mass (several times 10(10) M-circle dot) and metallicity (roughly solar). At redshift z = 0.031, Gaia17biu is also the lowest-redshift SLSN-I to date, and the absence of a larger population of SLSNe-I in dwarf galaxies of similar redshift suggests that metallicity is likely less important to the production of SLSNe-I than previously believed. With the smallest distance and highest apparent brightness for an SLSN-I, we are able to study Gaia17biu in unprecedented detail. Its pre-peak near-ultraviolet to optical color is similar to that of Gaia16apd and among the bluest observed for an SLSN-I, while its peak luminosity (M-g = -21 mag) is substantially lower than that of Gaia16apd. Thanks to the high signal-to-noise ratios of our spectra, we identify several new spectroscopic features that may help to probe the properties of these enigmatic explosions. We detect polarization at the similar to 0.5% level that is not strongly dependent on wavelength, suggesting a modest, global departure from spherical symmetry. In addition, we put the tightest upper limit yet on the radio luminosity of an SLSN-I with < 5.4 x 10(26) erg s(-1) Hz(-1) at 10 GHz, which is almost a factor of 40 better than previous upper limits and one of the few measured at an early stage in the evolution of an SLSN-I. This limit largely rules out an association of this SLSN-I with known populations of gamma-ray-burst-like central engines.</P>