11β-Hydroxysteroid dehydrogenases control access of 7β,27-dihydroxycholesterol to retinoid-related orphan receptor γ

Background: : One of the best known to date GPCR class A (Rhodopsin) includes more than 100 orphan receptors for which the endogenous ligand is not known or is unclear. One of them is N-arachidonyl glycine receptor, named GPR18, a receptor that has been reported to be activated by Δ9-THC, endogenous cannabinoid receptors agonist anandamide and other cannabinoid receptor ligands suggesting it could be considered as third cannabinoid receptor. GPR18 activity, as well as its distribution might suggest usage of GPR18 ligands in treatment of endometriosis, cancer, and neurodegenerative disorders. Yet, so far only few GPR18 antagonists have been described, thus only ligand-based design approaches appear to be most useful to identify new ligands for this orphan receptor. Methods: : Main goal of this study, GPR18 inactive form homology model was built on the basis of the evolutionary closest homologous template: Human P2Y1 Receptor crystal structure. Results: : Obtained model was further evaluated and showed active/nonactive ligands differentiating properties with acceptable confidence. Moreover, it allowed for preliminary assessment of proteinligand interactions for a set of previously described ligands. Conclusion:: Thus collected data might serve as a starting point for a discovery of novel, active GPR18 blocking ligands.

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Genomic Structure and Mapping of Human Orphan Receptor LXR Alpha : Upregulation of LXRa mRNA During Monocyte to Macrophage Differentiation

Journal of Atherosclerosis and Thrombosis ◽

10.5551/jat1994.7.145 ◽

2000 ◽

Vol 7 (3) ◽

pp. 145-151 ◽

Cited By ~ 31

Author(s):

Takahide Kohro ◽

Toshiaki Nakajima ◽

Yoichiroh Wada ◽

Akira Sugiyama ◽

Masami Ishii ◽

...

Keyword(s):

Genomic Structure ◽

Orphan Receptor ◽

Macrophage Differentiation

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Cutting Edge: Identification of the Orphan Receptor G-Protein-Coupled Receptor 2 as CCR10, a Specific Receptor for the Chemokine ESkine

The Journal of Immunology ◽

10.4049/jimmunol.164.7.3460 ◽

2000 ◽

Vol 164 (7) ◽

pp. 3460-3464 ◽

Cited By ~ 65

Author(s):

David I. Jarmin ◽

Miriam Rits ◽

Dalena Bota ◽

Norma P. Gerard ◽

Gerard J. Graham ◽

...

Keyword(s):

G Protein ◽

Cutting Edge ◽

Orphan Receptor ◽

Specific Receptor ◽

G Protein Coupled Receptor ◽

G Protein Coupled

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Ultrasensitive and label free electrochemical immunosensor for detection of ROR1 as an oncofetal biomarker using gold nanoparticles assisted LDH/rGO nanocomposite

Scientific Reports ◽

10.1038/s41598-021-94380-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rozita Abolhasan ◽

Balal Khalilzadeh ◽

Hadi Yousefi ◽

Sahar Samemaleki ◽

Forough Chakari-Khiavi ◽

...

Keyword(s):

Gold Nanoparticles ◽

Flexible Structures ◽

Modified Electrodes ◽

Electrochemical Immunosensor ◽

Lymphocytic Leukemia ◽

Orphan Receptor ◽

Detection Sensitivity ◽

Label Free ◽

Serum Samples ◽

Limit Of Quantification

AbstractIn the present article, we developed a highly sensitive label-free electrochemical immunosensor based on NiFe-layered double hydroxides (LDH)/reduced graphene oxide (rGO)/gold nanoparticles modified glassy carbon electrode for the determination of receptor tyrosine kinase-like orphan receptor (ROR)-1. In this electrochemical immunoassay platform, NiFe-LDH/rGO was used due to great electron mobility, high specific surface area and flexible structures, while Au nanoparticles were prepared and coated on the modified electrodes to improve the detection sensitivity and ROR1 antibody immobilizing (ROR1Ab). The modification procedure was approved by using cyclic voltammetry and differential pulse voltammetry based on the response of peak current to the step by step modifications. Under optimum conditions, the experimental results showed that the immunosensor revealed a sensitive response to ROR1 in the range of 0.01–1 pg mL−1, and with a lower limit of quantification of 10 attogram/mL (10 ag mL−1). Furthermore, the designed immunosensor was applied for the analysis of ROR1 in several serum samples of chronic lymphocytic leukemia suffering patients with acceptable results, and it also exhibited good selectivity, reproducibility and stability.

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The role of peripheral type 2 innate lymphoid cells in bronchiolitis

Scientific Reports ◽

10.1038/s41598-021-82096-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yong-Jun Tang ◽

Li-Li Xie ◽

Xiang-Rong Zheng ◽

Chen-Tao Liu ◽

Xia Wang

Keyword(s):

Statistical Significance ◽

Serum Levels ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Orphan Receptor ◽

Control Group ◽

Interleukin 5 ◽

Healthy Infants ◽

Significant Difference

AbstractOur aim was to detect type 2 innate lymphoid cells (ILC2s)-related cytokines of infants with bronchiolitis by using Elisa, Liquidchip technology and RT-PCR and investigated its correlation with bronchiolitis. We recruited 26 infants with bronchiolitis and 20 healthy infants as control from Xiangya Hospital. Compared to the control group, the serum levels of interleukin-5 (IL-5) [41.99 (21.11) vs 25.70 (19.64)], IL-9 [27.04 (37.51) vs 8.30 (0.54)], IL-13 [184.05 (132.81) vs 121.75 (176.13)], IL-33 [83.70 (46.69) vs 11.23 (55.31)] and thymic stromal lymphopoietin (TSLP) [31.42 (5.41) vs 28.76 (2.56)] were significantly increased in infants with bronchiolitis (P < 0.05), while the level of IgE had no significant difference between the two groups [19.05 (14.15) vs 14.85 (20.2), P > 0.05]. The mRNA expression of IL-17RB (9.83 ± 0.35 vs 9.19 ± 0.58), TSLP (16.98 ± 2.12 vs 15.07 ± 2.25), retinoid acid receptor related orphan receptor α (7.18 ± 0.71 vs 5.46 ± 1.09) and trans-acting T-cell-specific transcription factor 3 (4.86 ± 0.66 vs 4.19 ± 0.90) were significantly increased in infants with bronchiolitis versus the control group (P < 0.05), while there was no statistical significance for suppression of tumorigenicity 2 (5.59 ± 0.68 vs 5.41 ± 0.87, P > 0.05). Our findings suggested that ILC2s possibly play a specific role in immunopathology of bronchiolitis.

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Retraction Note: Orphan receptor ligand discovery by pickpocketing pharmacological neighbors

Nature Chemical Biology ◽

10.1038/s41589-021-00746-1 ◽

2021 ◽

Vol 17 (4) ◽

pp. 501-501 ◽

Cited By ~ 1

Author(s):

Tony Ngo ◽

Andrey V. Ilatovskiy ◽

Alastair G. Stewart ◽

James L. J. Coleman ◽

Fiona M. McRobb ◽

...

Keyword(s):

Orphan Receptor ◽

Receptor Ligand ◽

Ligand Discovery

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High retinoic acid receptor-related orphan receptor A gene expression in peripheral blood leukocytes may be related to acute myocardial infarction

Journal of International Medical Research ◽

10.1177/03000605211019663 ◽

2021 ◽

Vol 49 (6) ◽

pp. 030006052110196

Author(s):

Heyu Meng ◽

Jianjun Ruan ◽

Xiaomin Tian ◽

Lihong Li ◽

Weiwei Chen ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Acute Myocardial Infarction ◽

Coronary Artery ◽

Peripheral Blood ◽

Retinoic Acid Receptor ◽

Stable Coronary Artery Disease ◽

Orphan Receptor ◽

Blood Leukocytes ◽

Artery Disease

Objective This study aimed to investigate whether differential expression of the retinoic acid receptor-related orphan receptor A ( RORA) gene is related to occurrence of acute myocardial infarction (AMI). Methods This was a retrospective study. White blood cells of 93 patients with acute myocardial infarction and 74 patients with stable coronary artery disease were collected. Reverse transcription quantitative polymerase chain reaction and western blotting were used to measure RORA mRNA and protein expression, respectively. Results RORA mRNA expression levels in peripheral blood leukocytes in patients with AMI were 1.57 times higher than those in patients with stable coronary artery disease. Protein RORA levels in peripheral blood of patients with AMI were increased. Binary logistic regression analysis showed that high expression of RORA was an independent risk factor for AMI, and it increased the risk of AMI by 2.990 times. Conclusion RORA expression levels in patients with AMI is significantly higher than that in patients with stable coronary artery disease. High expression of RORA is related to AMI and it may be an independent risk factor for AMI.

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CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation

Blood ◽

10.1182/blood-2011-05-352682 ◽

2011 ◽

Vol 118 (23) ◽

pp. 6107-6114 ◽

Cited By ~ 36

Author(s):

Jelle de Wit ◽

Yuri Souwer ◽

Astrid J. van Beelen ◽

Rosa de Groot ◽

Femke J. M. Muller ◽

...

Keyword(s):

Th17 Cells ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Orphan Receptor ◽

The Novel ◽

Cd28 Costimulation ◽

Th17 Differentiation ◽

Novel Concept ◽

Transcription 3 ◽

Lymphocyte Receptors

Abstract IL-17–producing CD4+ T helper (Th17) cells are important for immunity against extracellular pathogens and in autoimmune diseases. The factors that drive Th17 development in human remain a matter of debate. Here we show that, compared with classic CD28 costimulation, alternative costimulation via the CD5 or CD6 lymphocyte receptors forms a superior pathway for human Th17-priming. In the presence of the Th17-promoting cytokines IL-1β, IL-6, IL-23, and transforming growth factor-β (TGF-β), CD5 costimulation induces more Th17 cells that produce higher amounts of IL-17, which is preceded by prolonged activation of signal transducer and activator of transcription 3 (STAT3), a key regulator in Th17 differentiation, and enhanced levels of the IL-17–associated transcription factor retinoid-related orphan receptor-γt (ROR-γt). Strikingly, these Th17-promoting signals critically depend on CD5-induced elevation of IL-23 receptor (IL-23R) expression. The present data favor the novel concept that alternative costimulation via CD5, rather than classic costimulation via CD28, primes naive T cells for stable Th17 development through promoting the expression of IL-23R.

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