scholarly journals Polyinosinic: Polycytidylic Acid and Murine Cytomegalovirus Modulate Expression of Murine IL-10 and IL-21 in White Adipose Tissue

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 569
Author(s):  
Pablo Garcia-Valtanen ◽  
Ruth Marian Guzman-Genuino ◽  
John D. Hayball ◽  
Kerrilyn R. Diener
Keyword(s):  
Adipose Tissue ◽  
B Cells ◽  
White Adipose Tissue ◽  
Ex Vivo ◽  
Interleukin 10 ◽  
Poly I:C ◽  
Murine Cytomegalovirus ◽  
Polycytidylic Acid ◽  
Polyinosinic Polycytidylic Acid

White adipose tissue (WAT) produces interleukin-10 and other immune suppressors in response to pathogen-associated molecular patterns (PAMPs). It also homes a subset of B-cells specialized in the production of IL-10, referred to as regulatory B-cells. We investigated whether viral stimuli, polyinosinic: polycytidylic acid (poly(I:C)) or whole replicative murine cytomegalovirus (MCMV), could stimulate the expression of IL-10 in murine WAT using in vivo and ex vivo approaches. Our results showed that in vivo responses to systemic administration of poly(I:C) resulted in high levels of endogenously-produced IL-10 and IL-21 in WAT. In ex vivo WAT explants, a subset of B-cells increased their endogenous IL-10 expression in response to poly(I:C). Finally, MCMV replication in WAT explants resulted in decreased IL-10 levels, opposite to the effect seen with poly(I:C). Moreover, downregulation of IL-10 correlated with relatively lower number of Bregs. To our knowledge, this is the first report of IL-10 expression by WAT and WAT-associated B-cells in response to viral stimuli.

Modulation of the prostaglandin responses of conscious rabbits to the pyrogen polyinosinic: polycytidylic acid by corticotrophin-releasing factor-41

1993 ◽  
Vol 138 (1) ◽  
pp. 7-11 ◽  
Author(s):  
N. G. N. Milton ◽  
E. W. Hillhouse ◽  
A. S. Milton
Keyword(s):  
Poly I:C ◽  
Lag Phase ◽  
Prostaglandin E ◽  
Interferon Inducer ◽  
Corticotrophin Releasing Factor ◽  
Polycytidylic Acid ◽  
Prostaglandin F ◽  
Conscious Rabbits ◽  
Polyinosinic Polycytidylic Acid

ABSTRACT The pyrogenic interferon inducer polyinosinic: polycytidylic acid (Poly I: C) was shown to stimulate rises in both prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in conscious rabbits in vivo. Poly I:C (2·5 μg/kg) stimulated a fivefold rise in circulating immunoreactive (ir) PGE2, with a lag phase of 60 min, which was sustained during the subsequent 4-h period of observation. Poly I:C also stimulated a 2·5-fold rise in circulating irPGF2α with a lag phase of 90 min, which was followed by a return to basal levels after 5 h. The rises in circulating irPGE2 and irPGF2α stimulated by Poly I:C were prevented by pretreatment with the non-steroidal anti-inflammatory drug ketoprofen. Both the irPGE2 and irPGF2α responses to Poly I:C (2·5 μg/kg, i.v.) were antagonized by the corticotrophin-releasing factor-41 (CRF-41) receptor antagonist (α-helical CRF (9–41), 25 μg/kg, i.v.) administered 5 min prior to the pyrogen. Peripheral immunoneutralization using an anti-CRF-41 monoclonal antibody (KCHMB001, 2·5 mg/kg, i.v.) administered 5 min prior to the pyrogen, also inhibited both the PGE2 and PGF2α responses to Poly I:C (2·5 μg/kg, i.v.). However, control mouse IgG also inhibited the PGE2 response. In conclusion, these results suggest a modulatory role for endogenous peripheral CRF-41 in the circulating prostaglandin responses to the pyrogen Poly I: C and this effect may be responsible for the antipyretic actions of peripherally administered CRF-41 antagonists and antibodies. Journal of Endocrinology (1993) 138, 7–11

Activation of the hypothalamo-pituitary-adrenocortical axis in the conscious rabbit by the pyrogen polyinosinic: polycytidylic acid is dependent on corticotrophin-releasing factor-41

1992 ◽  
Vol 135 (1) ◽  
pp. 69-75 ◽  
Author(s):  
N. G. N. Milton ◽  
E. W. Hillhouse ◽  
A. S. Milton
Keyword(s):  
Receptor Antagonist ◽  
Hpa Axis ◽  
Poly I:C ◽  
Prostaglandin E ◽  
Cortisol Response ◽  
Interferon Inducer ◽  
Corticotrophin Releasing Factor ◽  
Polycytidylic Acid ◽  
Polyinosinic Polycytidylic Acid

ABSTRACT The pyrogenic interferon inducer polyinosinic: polycytidylic acid (Poly I: C) was shown to activate the rabbit hypothalamo-pituitary-adrenocortical (HPA) axis in vivo. The immunoreactive cortisol response to Poly I:C (2·5 μg/kg) was shown to have a corticotrophin-releasing factor-41 (CRF-41)-dependent component which was abolished by peripheral immunoneutralization using an anti-CRF41 monoclonal antibody (KCHMB001; 2·5 mg/kg i.v.). Peripheral administration of the arginine vasopressin (AVP) V1 receptor antagonist ([deaminoPen1, O-Me-Tyr2, Arg8]-vasopressin; 225 nmol/kg i.v.) had no effect on the response of immunoreactive cortisol to Poly I:C, suggesting that AVP was not involved in activation of the HPA axis. Poly I: C increased both body temperature and circulating immunoreactive prostaglandin E2; these responses were abolished by the cyclo-oxygenase inhibitor ketoprofen (3 mg/kg s.c.). The immunoreactive cortisol response to Poly I: C, however, remained after the administration of ketoprofen, indicating a prostaglandin (PG)-independent component. The immunoreactive cortisol levels in control, saline vehicle-treated, animals were reduced by both the CRF-41 receptor antagonist (α-helical CRF (9–41); 6·25 mmol/kg i.v.) and ketoprofen (3 mg/kg s.c.) indicating that this basal state is dependent on both CRF-41 and PGs. Journal of Endocrinology (1992) 135, 69–75

scholarly journals Skeletal muscle tissue secretes more extracellular vesicles than white adipose tissue and myofibers are a major source ex vivo but not in vivo

2020 ◽  
Author(s):  
Andrea L. Estrada ◽  
Zackary Valenti ◽  
Gabriella Hehn ◽  
Christopher P. Allen ◽  
Nicole A. Kruh-Garcia ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
White Adipose Tissue ◽  
Ex Vivo ◽  
Fluorescent Reporter ◽  
Reporter Mouse ◽  
Relative Contribution ◽  
Human Protein Atlas

AbstractCirculating extracellular vesicles (EVs) are biomarkers of and contributors to the etiology of disease. Skeletal muscle (SkM) and white adipose tissue (WAT) are the two largest organs by mass in humans and rodents but the relative contribution of EVs from these tissues is unknown. We hypothesized that SkM tissue secretes more EVs than WAT and that a dual fluorescent reporter mouse could be used to detect SkM myofiber-derived EVs in vivo. Human Protein Atlas data and directly measuring EV secretion in mouse SkM and WAT using an ex vivo tissue explant model confirmed that SkM tissue secretes more EVs than WAT. Differences in EV secretion between SkM and WAT were not due to SkM contraction but may be explained by differences in tissue metabolic capacity. A SkM myofiber-specific dual fluorescent reporter mouse was created. Spectral flow cytometry revealed that SkM myofibers are a major source of SkM tissue-derived EVs ex vivo but few reach the circulation in vivo. Our findings demonstrate that SkM secretes more EVs than WAT and many come from SkM myofibers, but our in vivo data indicate that EVs secreted by SkM myofibers may remain primarily in their local extracellular environment.

scholarly journals In Vivo Response to α1-Adrenoreceptor Stimulation in Human White Adipose Tissue

2002 ◽  
Vol 10 (6) ◽  
pp. 555-558 ◽  
Author(s):  
Michael Boschmann ◽  
Götz Krupp ◽  
Friedrich C. Luft ◽  
Susanne Klaus ◽  
Jens Jordan
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue

IMMU-29. B-CELL-BASED VACCINE PRODUCES GLIOBLASTOMA-REACTIVE ANTIBODIES THAT CONTRIBUTE TO TUMOR CLEARANCE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi98-vi98
Author(s):  
Brandyn Castro ◽  
Mark Dapash ◽  
David Hou ◽  
Aida Rashidi ◽  
Deepak Kanojia ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Ex Vivo ◽  
Murine Models ◽  
Effector Functions ◽  
Tumor Bearing ◽  
Tumor Clearance ◽  
Cellular And Humoral Immunity

Abstract Glioblastomas (GBM) are characterized by a strong immunosuppressive environment, contributing to their poor prognosis and limited therapeutic response to immunotherapies. B-cells represent a unique opportunity to promote immunotherapy due to their potential to kill tumors by both cellular and humoral immunity. To generate our B-cell-based vaccine (BVax) platform, we activated 41BBL+ B cells from tumor bearing mice or GBM patient blood with BAFF, CD40, and IFNg. We have previously demonstrated that BVax potentiates radiation therapy, temozolomide and checkpoint blockade in murine models of GBM via enhancement of CD8+ T-cell based immunity. The aim of this current study is to evaluate the humoral effector functions of BVax. We examined the antibody (Ab) repertoire in vivo from serum of tumor-bearing B-cell knockout mice treated with BVax or by ex vivo stimulation of patient-derived BVax. Upon systemic administration, BVax infiltrates the tumor where it differentiates into plasmablasts. Murine BVax- and BNaive-derived serum immunoglobulin generated in vivo showed that the majority of murine BVax-derived Ab were IgG isotype, while BNaive mainly produced IgM isotype. Transfer of IgG from BVax treated mice directly into tumors of recipient animals significantly prolonged their survival, demonstrating anti-tumor cytotoxicity directly through humoral immunity. Patient-derived BVax activated ex vivo showed a plasmablast phenotype and the Ab repertoire supports the previous findings seen in our murine model. Our work suggests BVax-derived IgGs role in antibody-dependent cellular cytotoxicity and improved survival in murine models. This function, in addition to its role in cellular immunity against GBM, renders BVax a potentially effective alternative immunotherapeutic option for GBM patients.

Catecholaminergic innervation of white adipose tissue in Siberian hamsters

1995 ◽  
Vol 268 (3) ◽  
pp. R744-R751 ◽  
Author(s):  
T. G. Youngstrom ◽  
T. J. Bartness
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Neural Control ◽  
Fat Pad ◽  
Anterograde Transport ◽  
Siberian Hamsters ◽  
Lipid Stores ◽  
Catecholaminergic Innervation ◽  
Fat Pads

When Siberian hamsters are transferred from long summerlike days (LDs) to short winterlike days (SDs) they decrease their body weight, primarily as body fat. These SD-induced decreases in lipid stores are not uniform. Internally located white adipose tissue (WAT) pads are depleted preferentially of lipid, whereas the more externally located subcutaneous WAT pads are relatively spared. These data suggest a possible differential sympathetic neural control over catecholamine-induced lipolysis and that lipolytic rates are greater for internal vs. external WAT pads. Moreover, if these differential rates of lipolysis are due to differential sympathetic nervous system (SNS) drives on the pads, then fat pad-specific catecholaminergic innervation may exist. Therefore, we tested whether inguinal WAT (IWAT; an external pad) and epididymal WAT (EWAT; an internal pad) were innervated differentially. In addition, we tested whether norepinephrine (NE) turnover (TO) reflected the presumed greater SNS drive on EWAT vs. IWAT after SD exposure. Injections of fluorescent tract tracers [Fluoro-Gold or indocarbocyanine perchlorate (DiI)] demonstrated projections from the SNS ganglia T13-L3 to both fat pads. Retrograde labeling revealed a relatively separate pattern of distribution of labeled neurons in the ganglia projecting to each pad. In vivo anterograde transport of DiI resulted in labeling in both IWAT and EWAT that included staining around individual adipocytes and occasionally retrogradely labeled cells. The proportionately greater decrease in EWAT compared with IWAT mass after 5 wk of SD exposure was reflected in greater EWAT NE TO than found in their LD counterparts for this pad.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals My D88-Dependent Interplay Between Myeloid and Endothelial Cells in the Initiation and Progression of Obesity-Associated Inflammatory Diseases

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. SCI-44-SCI-44
Author(s):  
Xiaoxia Li
Keyword(s):  
Insulin Resistance ◽  
Endothelial Cells ◽  
Adipose Tissue ◽  
Systemic Inflammation ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Low Grade

Abstract Low-grade systemic inflammation is often associated with metabolic syndrome, which plays a critical role in the development of the obesity-associated inflammatory diseases, including insulin resistance and atherosclerosis. Here, we investigate how Toll-like receptor-MyD88 signaling in myeloid and endothelial cells coordinately participates in the initiation and progression of high fat diet-induced systemic inflammation and metabolic inflammatory diseases. MyD88 deficiency in myeloid cells inhibits macrophage recruitment to adipose tissue and their switch to an M1-like phenotype. This is accompanied by substantially reduced diet-induced systemic inflammation, insulin resistance, and atherosclerosis. MyD88 deficiency in endothelial cells results in a moderate reduction in diet-induced adipose macrophage infiltration and M1 polarization, selective insulin sensitivity in adipose tissue, and amelioration of spontaneous atherosclerosis. Both in vivo and ex vivo studies suggest that MyD88-dependent GM-CSF production from the endothelial cells might play a critical role in the initiation of obesity-associated inflammation and development of atherosclerosis by priming the monocytes in the adipose and arterial tissues to differentiate into M1-like inflammatory macrophages. Collectively, these results implicate a critical MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for Atopic Dermatitis (AD) treatment

2021 ◽  
Author(s):  
Audrey Baylet ◽  
Raoul Vyumvuhore ◽  
Marine Laclaverie ◽  
Laëtitia Marchand ◽  
Carine Mainzer ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
Topical Therapy ◽  
Human Keratinocytes ◽  
Raman Microspectroscopy ◽  
Poly I:C ◽  
Interleukin 4 ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Polycytidylic Acid

SummaryBackgroundCurrently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis (PSO) or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin.ObjectivesThe aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4).MethodsTranscutaneous penetration was evaluated by ex vivo studies on tape-stripped pig ear skin. Antibody visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied using two 2D models. First, embryonic alkaline phosphatase (SEAP) secretion by HEK-Blue™ IL-4/IL-13 cells, proportional to hIL-4 cells stimulation, was quantified by OD 620 nm measurement in presence or absence of an anti-hIL4 scFv or Ab. Then, normal human keratinocytes (NHKs) were stimulated with polyinosinic-polycytidylic acid (poly I:C) +/− hIL-4 and treated with anti-hIL4 scFv. Human Interleukin-8 (hIL-8) concentrations were determined in culture supernatants by ELISA.ResultsAfter 24h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on the stratum corneum. In addition, the anti-hIL4 scFv showed better efficiency compared to Ab, with a neutralization percentage at 200 nM of 68% and 47%, respectively, in the HEK-Blue™ IL-4/IL-13 model. hIL-8 dosage in stimulated NHKs supernatants revealed that addition of scFv induced a dose-dependent hIL-4 neutralization.ConclusionsscFv penetrates through to the upper papillary dermis while Ab remains on the surface. The anti-hIL4 scFv neutralizes its target effectively in two 2D models suggesting its potential use as topical therapy for AD.

scholarly journals Multinucleated giant cells in adipose tissue are specialized in adipocyte degradation

2020 ◽  
Author(s):  
Ada Admin ◽  
Julia Braune ◽  
Andreas Lindhorst ◽  
Janine Fröba ◽  
Constance Hobusch ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Ex Vivo ◽  
Giant Cells ◽  
Low Grade ◽  
Adipose Tissue Macrophages ◽  
Visceral Adipose ◽  
Low Grade Inflammation

Obesity is associated with a chronic low-grade inflammation in visceral adipose tissue (AT) characterized by an increasing number of adipose tissue macrophages (ATMs) and linked to type 2 diabetes. AT inflammation is histologically indicated by the formation of so-called crown-like structures (CLS), as accumulation of ATMs around dying adipocytes, and the occurrence of multi-nucleated giant cells (MGCs). However to date, the function of MGCs in obesity is unknown. Hence, the aim of this study was to characterize MGCs in AT and unravel the function of these cells. <p>We demonstrate that MGCs occur in obese patients and after 24 weeks of high fat diet (HFD) in mice, accompanying signs of AT inflammation and then represent ~3% of ATMs in mice. Mechanistically, we found evidence that adipocyte death triggers MGC formation. Most importantly, MGCs in obese AT have a higher capacity to phagocytose oversized particles, such as adipocytes, as shown by live-imaging of AT, 45 µm bead uptake <i>ex vivo</i> and a higher lipid content <i>in vivo</i>. Finally, we show that IL-4 treatment is sufficient to increase the number of MGCs in AT, whereas other factors maybe more important for endogenous MGC formation <i>in vivo</i>.</p>

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