scholarly journals Mediation of interleukin-11-dependent biological responses by a soluble form of the interleukin-11 receptor

1996 ◽  
Vol 318 (2) ◽  
pp. 489-495 ◽  
Author(s):  
Julia KAROW ◽  
Keith R. HUDSON ◽  
Mark A. HALL ◽  
Ann B. VERNALLIS ◽  
Jacky A. TAYLOR ◽  
...  
Keyword(s):  
Biological Effects ◽  
Biological Response ◽  
Cytoplasmic Domain ◽  
Soluble Form ◽  
High Affinity ◽  
Biological Responses ◽  
Interleukin 11 ◽  
Biological Actions ◽  
In Cells

Interleukin-11 (IL-11) is a polyfunctional cytokine whose biological actions require a specific IL-11 receptor (IL-11R) and the transmembrane transducer gp130. Here we report the production of a soluble form of the murine IL-11R and demonstrate that it interacts with IL-11 ligand with high affinity. The affinity of IL-11 alone for gp130 is below the level of detection, but a complex of IL-11 and soluble IL-11R interacts with gp130 with high affinity. The addition of soluble IL-11R potentiates the effects of exogenous IL-11 in cells that are normally responsive to IL-11. A biological response to IL-11 can be reconstituted in BAF cells transfected with gp130 by addition of IL-11 and soluble IL-11R. These findings show that the cytoplasmic domain of the IL-11R is not required for the biological effects of IL-11 and that a complex of IL-11 and IL-11R mediates signalling by association with gp130.

scholarly journals Targeting of the Pilosebaceous Follicle by Liquid Crystal Nanocarriers: In Vitro and In Vivo Effects of the Entrapped Minoxidil

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1127
Author(s):  
Massimo Fresta ◽  
Antonia Mancuso ◽  
Maria Chiara Cristiano ◽  
Konrad Urbanek ◽  
Felisa Cilurzo ◽  
...  
Keyword(s):  
Liquid Crystal ◽  
Biological Effects ◽  
Biological Response ◽  
Response Duration ◽  
Topical Administration ◽  
Active Compounds ◽  
Biological Responses ◽  
Negative Surface

The topical administration of active compounds represents an advantageous strategy to reach the various skin components as well as its appendages. Pilosebaceous follicles are skin appendages originating in the deeper skin layers. They are very difficult to target, and hence higher active dosages are generally required to achieve effective biological responses, thus favoring the rise of side effects. The aim of this work was to design a supramolecular colloidal carrier, i.e., a liquid crystal nanocarrier, for the selective delivery of active compounds into the pilosebaceous follicle. This nanocarrier showed mean sizes of ~80 nm, a good stability, a negative surface charge, and great safety properties. In vitro studies highlighted its ability to contain and release different substances and to successfully permeate the skin. Minoxidil was encapsulated in the nanocarriers and the in vivo biological effect was compared with a conventional dosage form. Minoxidil-loaded liquid crystal nanocarrier was able to selectively reach the pilosebaceous follicle, thus allowing an increased biological effectiveness of the delivered active in terms of biological response, duration of the biological effects, and reduction of collaterals. Our investigation showed that liquid crystal nanocarriers represent a promising device for the treatment of different pilosebaceous follicular impairments/diseases.

scholarly journals Blockade of Growth Hormone Receptor Shedding by a Metalloprotease Inhibitor*

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1927-1935 ◽  
Author(s):  
Jimmy Alele ◽  
Jing Jiang ◽  
Jeffrey F. Goldsmith ◽  
Xiaoyong Yang ◽  
Hiralal G. Maheshwari ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Growth Hormone Receptor ◽  
Biological Effects ◽  
Extracellular Domain ◽  
Cytoplasmic Domain ◽  
Full Length ◽  
Soluble Form ◽  
Rapid Loss ◽  
Minimum Effective Concentration ◽  
Metalloprotease Inhibitor

Abstract GH, an important growth-promoting and metabolic hormone, exerts its biological effects by interacting with cell surface GH receptors (GHRs). The GHR is a single membrane-spanning protein that binds GH via its extracellular domain. The high affinity GH-binding protein (GHBP), which corresponds to a soluble form of the GHR extracellular domain, carries a substantial fraction of the GH in the circulation of various species and probably has a role in modulation of the hormone’s bioavailability. Although in rodents, it is believed that the GHBP is largely derived by translation of an alternatively spliced GHR messenger RNA, in humans and rabbits, proteolytic cleavage of the membrane-anchored receptor releases the GHR extracellular domain, which is believed to thereby become the GHBP. In this study, we used human IM-9 lymphocytes and GHR antibodies to study this proteolytic shedding of the GHBP. As determined by immunoblotting with anti-GHR cytoplasmic domain serum, addition of phorbol 12-myristate 13-acetate (PMA; 1μ g/ml) to serum-starved cells led to rapid loss (roughly 60% decline after 1 h; t1/2 = ∼5 min) of mature GHRs (115–140 kDa) from either total cell or detergent-soluble extracts. Loss of full-length GHRs was accompanied by accumulation of four proteins (65–68 kDa), each reactive with the cytoplasmically directed antiserum. The pattern of appearance of these GHR ctyoplasmic domain proteins, the electrophoretic and immunological characteristics of which are similar to those of a recombinant rabbit GHR mutant that lacks the extracellular domain, was such that progressively faster migrating forms were evident between 5–60 min of PMA exposure. Treatment with N-ethylmaleimide (NEM; 5 mm), an agent known to cause GHBP shedding from IM-9 cells, promoted a similar rapid loss of full-length GHRs and an accumulation of GHR cytoplasmic domain remnant proteins. PMA-induced, but not NEM-induced, GHR proteolysis was blocked by the protein kinase C inhibitor, GF109203X. Both PMA- and NEM-induced receptor proteolysis were, however, inhibited by the metalloprotease inhibitor, Immunex Compound 3 (minimum effective concentration, 10 μm). Notably, PMA and NEM also promoted shedding of GHBP into the conditioned medium of the cells, as determined by a chromatographic [125I]human GH binding assay; this GHBP shedding was also inhibited by Immunex Compound 3. These results strongly implicate a member(s) of the metalloprotease family as a potential GHBP-generating enzyme.

scholarly journals Integrated Biomarker Response for Environmental Assessment Using the Gastropod Phorcus turbinatus along the Northern and the Northeastern Coasts of Tunisia

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 529
Author(s):  
Wafa Boulajfene ◽  
Montassar Lasram ◽  
Sabiha Zouari-Tlig
Keyword(s):  
Condition Factor ◽  
Monitoring Program ◽  
Biological Response ◽  
Temporal Variations ◽  
Chemical Pollution ◽  
Glutathione S Transferase ◽  
Biological Responses ◽  
Biomarker Response ◽  
Polycyclic Aromatic ◽  
Bio Monitoring

This work aims to assess the spatial and temporal variations of four biomarkers activities and to integrate their biological responses in a battery using the gastropod Phorcus turbinatus. The monitoring was carried out during the period between April 2014 and January 2015 at six stations along the northern and the northeastern coasts of Tunisia. The Fulton condition factor was estimated and the activities of catalase, acetylcholinesterase and glutathione-S-transferase were evaluated by spectrophotometry. A multi-biomarker battery approach was used to assess ecosystems’ condition and to identify environmental impacts on the organisms. The results suggest that the enzymatic activities of CAT and GST depend especially on seasons. As for AChE activity, it was similar between seasons and stations. The values of the integrated biological response were maximal at Jarzouna in summer and at Sidi Daoued in winter, indicating the presence of severe stressors suffered by the organisms. This perturbation may be due to the enrichment of the waters by xenobiotics, namely polycyclic aromatic hydrocarbons, insecticides, phosphate wastes, PCBs and pesticides. Thus, P. turbinatus seems to be a good bioindicator of chemical pollution, constituting an adequate tool for a bio-monitoring program.

scholarly journals Recombinant Soluble Interleukin-11 (IL-11) Receptor α-Chain Can Act as an IL-11 Antagonist

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4403-4412 ◽  
Author(s):  
David J. Curtis ◽  
Douglas J. Hilton ◽  
Bronwyn Roberts ◽  
Leecia Murray ◽  
Nicos Nicola ◽  
...  
Keyword(s):  
Leukemic Cells ◽  
Α Chain ◽  
Interleukin 11 ◽  
In Cells

We have expressed a soluble N-glycosylated form of the murine interleukin-11 (IL-11) receptor α-chain (sIL-11R) and examined signaling in cells expressing the gp130 molecule. In the presence of gp130 but not the transmembrane IL-11R, the sIL-11R mediated IL-11–dependent differentiation of M1 leukemic cells and proliferation in Ba/F3 cells. Early intracellular events stimulated by the sIL-11R including phosphorylation of gp130, STAT 3, and SHP-2 were similar to signaling through the transmembrane IL-11R. IL-11 bound to sIL-11R with low affinity (kd 10 to 50 nmol/L). Binding of sIL-11R to gp130 was IL-11 dependent with intermediate affinity (kd 1.5 to 3.0 nmol/L). However, the concentration of IL-11 required for signaling through the sIL-11R was 10- to 20-fold greater than that required for cells expressing the transmembrane IL-11R and gp130 in the absence of sIL-11R. Furthermore, the sIL-11R was capable of antagonizing the activity of IL-11 when tested on cells expressing the transmembrane IL-11R and gp130. We propose that the observed IL-11 antagonism by the sIL-11R may depend on limiting numbers of gp130 molecules on cells already expressing the transmembrane IL-11R.

scholarly journals 24 Condensed tannins: structure, activity and characterization

2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 21-22
Author(s):  
Wayne Zeller
Keyword(s):  
Condensed Tannins ◽  
Positive Impact ◽  
Biological Effects ◽  
Biological Response ◽  
Structural Diversity ◽  
Agricultural Industry ◽  
Structure Activity ◽  
Ct Analysis ◽  
Ruminal Digestion

Abstract As a class of plant polyphenolic compounds contained in some forages [i.e., sainfoin (Onobrychis viciifolia Scop.), big trefoil (Lotus pedunculatus Cav.), birdsfoot trefoil (Lotus corniculatus L.)], condensed tannins (CTs) exhibit a variety of biological effects on ruminants. The potential positive impact of CTs on the agricultural industry stems from their ability to modulate proteolysis during forage conservation and ruminal digestion, to prevent bloat, to reduce intestinal parasite burdens, and to abate methane and ammonia emissions from ruminants. How CTs exert these effects on ruminants focuses on the interaction of CTs with proteins. The structure-activity relationship in CT–protein interaction is not well understood but is known to be dependent on the structure and properties of both the CT and the protein. The objectives of this presentation are fivefold. First, examples of the structural diversity of CTs will be provided to enable the audience members to appreciate that not all CTs are the same. Second, examples of how CTs structural diversity affects their interaction with the protein, which in turn, dictates the biological response from the animal will be discussed. Third, the presentation will outline hurdles in obtaining highly pure and well-characterized CTs from natural sources for use in CT structural analysis and in vitro experiments. This will be followed by brief descriptions of improved and emerging techniques for CT analysis and, finally, the presentation concludes with questions to address in future investigations and a list of recommendations for CT researchers to follow.

scholarly journals EVALUATION OF TOXIC EFFECTS OF MAGNETIC CONTRAST DIAGNOSTIC GADOLINIUM-CONTAINING NANOCOMPOSITE

2019 ◽  
Vol 98 (10) ◽  
pp. 1161-1165
Author(s):  
Larisa M. Sosedova ◽  
E. A. Titov ◽  
M. A. Novikov ◽  
V. A. Vokina ◽  
V. S. Rukavishnikov
Keyword(s):  
Nervous Tissue ◽  
Chemical Elements ◽  
Biological Effects ◽  
Experimental Studies ◽  
Biological Response ◽  
Immunohistochemical Method ◽  
Ether Anesthesia ◽  
Compensatory Response ◽  
White Rats ◽  
Liver And Kidney

Introduction. In recent years, magnetic nanoparticles, which can simultaneously have a therapeutic effect on the pathological focus, are used to magnify contrast enhancement and increase diagnostic sensitivity during magnetic resonance therapy (MRT). The last is carried out by the effective capture of neutrons, which among all the chemical elements is most pronounced in gadolinium. The use of gadolinium nanoparticles encapsulated in a polymeric matrix allows increasing the bioavailability of nanoparticles, reduces the possible toxicity of drugs. Aim. Evaluation of impact of new nanocomposite magnetically active metal complex gadolinium system on the morphofunctional state of the nervous tissue, liver, and kidney of rats. Material and methods. Experimental studies of biological effects of gadolinium-arabinogalactan nanocomposite (Gd-AG) were carried out on rats that were injected intraperitoneally for 10 days at the dose of 500 μg/kg in 0.5 ml of saline. Animals were sacrificed by decapitation under light ether anesthesia the next day after the end of exposure. To perform pathological studies, frontal sections of the temporal-parietal zone of the sensorimotor cortex, liver and kidney tissues were stained on ordinary histological glass slides with hematoxylin and eosin for viewing microscopic picture. The immunohistochemical method was used to determine the activity of the bcl-2, caspase-3 and hsp70 modulatory protein in apoptosis of white rats in brain neurons and to study the biological response of the organism at the subcellular level. Results. Histological analysis of tissues revealed a pronounced compensatory response of liver, a violation of the functional activity of kidneys. A decrease in the total number of normal neurons per unit area in brain tissue and an increase in the number of acts of neuronophagy indicate the initial stage of neurodegenerative process. Evaluation of the intracellular metabolism of neurons has not established the presence of signs characteristic of apoptotic process. Conclusion. The subacute effect of Gd-AG in a dose of 500 µg/kg causes a disturbance of morphofunctional state of liver, kidneys and nervous tissue, as well as modulation of cellular proteomics.

scholarly journals Individual multi-locus heterozygosity is associated with lower morning plasma cortisol concentrations

2013 ◽  
Vol 169 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Lina Zgaga ◽  
Veronique Vitart ◽  
Caroline Hayward ◽  
Darko Kastelan ◽  
Ozren Polašek ◽  
...  
Keyword(s):  
Psychological Distress ◽  
Microsatellite Markers ◽  
Psychological Stress ◽  
Plasma Cortisol ◽  
Allostatic Load ◽  
General Health Questionnaire ◽  
Biological Response ◽  
Biological Responses ◽  
Likert Score ◽  
Morning Cortisol

ObjectiveStress is implicated as a risk factor for numerous illnesses in humans, putatively in part mediated by biological responses to stress, such as elevated cortisol concentrations. The theory of genetic homoeostasis suggests that individual heterozygosity facilitates compensation for environmental stresses. We hypothesized that heterozygosity ameliorates the biological response to a given level of perceived stress, reflected in lower plasma cortisol concentrations.DesignWe examined the role of heterozygosity in the association between perceived psychological stress and morning cortisol concentrations in 854 individuals from the isolated island of Vis, Croatia.MethodsCortisol concentrations were measured in morning plasma samples. A total of 1184 autosomal microsatellite markers were genotyped and individual multi-locus heterozygosity (MLH) was calculated as the proportion of heterozygous markers. The General Health Questionnaire with 30 items (GHQ-30) was used to assess the degree of psychological distress.ResultsMean MLH was 34.85±0.45% (range: 31.97–36.22%). Psychological distress (GHQ Likert score >31) was more prevalent in women (37 vs 18% in men, P<0.0001), in less educated people (β=−0.35 per year in school, P<0.001) and in lower socio-economic classes (β=−3.59, P<0.0001). Cortisol concentrations were positively associated with psychological distress (β=2.20, P=0.01). In a regression model adjusted for age, BMI, education and GHQ-30 score, MLH was independently and inversely associated with morning plasma cortisol concentrations (P=0.005).ConclusionMore heterozygous individuals, as measured by microsatellite markers, had lower morning plasma cortisol concentrations for a given level of perceived psychological stress. This may be important, as higher cortisol concentrations may increase the allostatic load and be associated with a higher risk of stress-related illness.

scholarly journals Methylation of deoxyribonucleic acid in cultured mammalian cells by N-methyl-N′-nitro-N-nitrosoguanidine. The influence of cellular thiol concentrations on the extent of methylation and the 6-oxygen atom of guanine as a site of methylation

1970 ◽  
Vol 116 (4) ◽  
pp. 693-707 ◽  
Author(s):  
P. D. Lawley ◽  
Carolyn J. Thatcher
Keyword(s):  
Oxygen Atom ◽  
Nucleic Acids ◽  
Mammalian Cells ◽  
Dimethyl Sulphate ◽  
Biological Effects ◽  
Methylation Of Dna ◽  
Thiol Content ◽  
Cellular Thiol ◽  
In Cells

1. In neutral aqueous solution N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) yields salts of nitrocyanamide as u.v.-absorbing products. With cysteine, as found independently by Schulz & McCalla (1969), the principal product is 2-nitràminothiazoline-4-carboxylic acid. Both these reactions liberate the methylating species; thiols enhance the rate markedly at neutral pH values. An alternative reaction with thiols gives cystine, presumably via the unstable S-nitrosocysteine. 2. Thiols (glutathione or N-acetylcysteine) in vitro at about the concentration found in mammalian cells enhance the rate of methylation of DNA markedly over that in neutral solution. 3. Treatment of cultured mammalian cells with MNNG results in rapid methylation of nucleic acids, the extent being greater the higher the thiol content of the cells. Rodent embryo cells are more extensively methylated than mouse L-cells of the same thiol content. Cellular thiol concentrations are decreased by MNNG. Proteins are less methylated by MNNG than are nucleic acids. 4. Methylation of cells by dimethyl sulphate does not depend on cellular thiol content and protein is not less methylated than nucleic acids. Methylation by MNNG may therefore be thiol-stimulated in cells. 5. Both in vitro and in cells about 7% of the methylation of DNA by MNNG occurs at the 6-oxygen atom of guanine. The major products 7-methylguanine and 3-methyladenine are given by both MNNG and dimethyl sulphate, but dimethyl sulphate does not yield O6-methylguanine. Possible reaction mechanisms to account for this difference between these methylating agents and its possible significance as a determinant of their biological effects are discussed.

scholarly journals Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway.

1996 ◽  
Vol 135 (1) ◽  
pp. 37-51 ◽  
Author(s):  
M Hirao ◽  
N Sato ◽  
T Kondo ◽  
S Yonemura ◽  
M Monden ◽  
...  
Keyword(s):  
Ionic Strength ◽  
Cytoplasmic Domain ◽  
Insoluble Fraction ◽  
Regulation Mechanism ◽  
Erm Proteins ◽  
Bhk Cells ◽  
High Affinity ◽  
Binding Partners

The ERM proteins, ezrin, radixin, and moesin, are involved in the actin filament/plasma membrane interaction as cross-linkers. CD44 has been identified as one of the major membrane binding partners for ERM proteins. To examine the CD44/ERM protein interaction in vitro, we produced mouse ezrin, radixin, moesin, and the glutathione-S-transferase (GST)/CD44 cytoplasmic domain fusion protein (GST-CD44cyt) by means of recombinant baculovirus infection, and constructed an in vitro assay for the binding between ERM proteins and the cytoplasmic domain of CD44. In this system, ERM proteins bound to GST-CD44cyt with high affinity (Kd of moesin was 9.3 +/- 1.6nM) at a low ionic strength, but with low affinity at a physiological ionic strength. However, in the presence of phosphoinositides (phosphatidylinositol [PI], phosphatidylinositol 4-monophosphate [4-PIP], and phosphatidylinositol 4.5-bisphosphate [4,5-PIP2]), ERM proteins bound with a relatively high affinity to GST-CD44cyt even at a physiological ionic strength: 4,5-PIP2 showed a marked effect (Kd of moesin in the presence of 4,5-PIP2 was 9.3 +/- 4.8 nM). Next, to examine the regulation mechanism of CD44/ERM interaction in vivo, we reexamined the immunoprecipitated CD44/ERM complex from BHK cells and found that it contains Rho-GDP dissociation inhibitor (GDI), a regulator of Rho GTPase. We then evaluated the involvement of Rho in the regulation of the CD44/ERM complex formation. When recombinant ERM proteins were added and incubated with lysates of cultured BHK cells followed by centrifugation, a portion of the recombinant ERM proteins was recovered in the insoluble fraction. This binding was enhanced by GTP gamma S and markedly suppressed by C3 toxin, a specific inhibitor of Rho, indicating that the GTP form of Rho in the lysate is required for this binding. A mAb specific for the cytoplasmic domain of CD44 also markedly suppressed this binding, identifying most of the binding partners for exogenous ERM proteins in the insoluble fraction as CD44. Consistent with this binding analysis, in living BHK cells treated with C3 toxin, most insoluble ERM proteins moved to soluble compartments in the cytoplasm, leaving CD44 free from ERM. These findings indicate that Rho regulates the CD44/ERM complex formation in vivo and that the phosphatidylinositol turnover may be involved in this regulation mechanism.

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