Endotoxin impedes vasoconstriction in the spleen: role of endogenous interleukin-1 and sympathetic innervation

1997 ◽  
Vol 272 (6) ◽  
pp. R2048-R2054 ◽  
Author(s):  
H. Rogausch ◽  
A. del Rey ◽  
A. Kabiersch ◽  
W. Reschke ◽  
J. Ortel ◽  
...  
Keyword(s):  
Blood Supply ◽  
Immune Cell ◽  
Interleukin 1 ◽  
Sympathetic Innervation ◽  
Nerve Fibers ◽  
Lymphoid Organs ◽  
Tight Control ◽  
Sympathetic Nerve Fibers

Processes relevant for an appropriate immune response such as immune cell traffic and recirculation require a tight control of blood supply to lymphoid organs. Interactions between endogenous cytokines and sympathetic nerve fibers in lymphoid organs can contribute to this control. The results reported in this paper show that 1) administration of low doses of lipopolysaccharide (LPS), an endotoxin derived from gram-negative bacteria, causes an increase in splenic blood flow (SBF); 2) this increase is mediated by the production of endogenous interleukin-1 (IL-1); 3) the effect of LPS on SBF requires an intact splenic sympathetic innervation; 4) the LPS-induced increase in SBF is exerted at the postganglionic level; 5) the endotoxin inhibits the vasoconstriction induced by the in vivo stimulation of the splenic nerve but does not affect the vasoconstriction induced by norepinephrine (NE); and 6) although IL-1 and LPS stimulate general sympathetic activity as reflected by increased peripheral vascular resistance, they do not increase NE concentration in splenic dialysates. Together these in vivo results indicate that endogenous IL-1 affects blood supply to the spleen by inhibiting the sympathetic vasoconstrictor tonus at a postganglionic, prejunctional level. This effect is expected to be relevant for immune cell recirculation, homing, and traffic as well as antigen trapping in the spleen, an organ specialized in the control of these processes during immune responses.

VEGF promotes vascular sympathetic innervation

2008 ◽  
Vol 294 (6) ◽  
pp. H2646-H2652 ◽  
Author(s):  
Stephen B. Marko ◽  
Deborah H. Damon
Keyword(s):  
Blood Vessels ◽  
Sympathetic Innervation ◽  
Nerve Fibers ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Sympathetic Nerve Fibers ◽  
Endothelial Growth Factor ◽  
Immunohistochemical Analyses

The sympathetic nervous system, via postganglionic innervation of blood vessels and the heart, is an important determinant of cardiovascular function. The mechanisms underlying sympathetic innervation of targets are not fully understood. This study tests the hypothesis that target-derived vascular endothelial growth factor (VEGF) promotes sympathetic innervation of blood vessels. Western blot and immunohistochemical analyses indicate that VEGF is produced by vascular cells in arteries and that VEGF receptors are expressed on sympathetic nerve fibers innervating arteries. In vitro, exogenously added VEGF and VEGF produced by vascular smooth muscle cells (VSMCs) in sympathetic neurovascular cocultures inhibited semaphorin 3A (Sema3A)-induced collapse of sympathetic growth cones. In the absence of Sema3A, VEGF and VSMCs also increased growth cone area. These effects were mediated via VEGF receptor 1. In vivo, the neutralization of VEGF inhibited the reinnervation of denervated femoral arteries. These data demonstrate that target-derived VEGF plays a previously unrecognized role in promoting the growth of sympathetic axons.

scholarly journals The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382199528
Author(s):  
Qing Lv ◽  
Qinghua Xia ◽  
Anshu Li ◽  
Zhiyong Wang
Keyword(s):  
Tumor Microenvironment ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
Stomach Carcinoma ◽  
Downstream Target ◽  
Volume Weight

This study was performed to investigate the role of interleukin-1 receptor accessory protein (IL1RAP) in stomach carcinoma in vitro and in vivo, determine whether IL1RAP knockdown could regulate the development of stomach carcinoma, and elucidate the relationship between IL1RAP knockdown and inflammation by tumor microenvironment-related inflammatory factors in stomach carcinoma. We first used TCGA and GEPIA systems to predict the potential function of IL1RAP. Second, western blot and RT-PCR were used to analyze the expression, or mRNA level, of IL1RAP at different tissue or cell lines. Third, the occurrence and development of stomach carcinoma in vitro and in vivo were observed by using IL1RAP knockdown lentivirus. Finally, the inflammation of stomach carcinoma in vitro and in vivo was observed. Results show that in GEPIA and TCGA systems, IL1RAP expression in STAD tumor tissue was higher than normal, and high expression of IL1RAP in STAD patients had a worse prognostic outcome. Besides, GSEA shown IL1RAP was negative correlation of apopopsis, TLR4 and NF-κB signaling pathway. We also predicted that IL1RAP may related to IL-1 s, IL-33, and IL-36 s in STAD. The IL1RAP expression and mRNA level in tumor, or MGC803, cells were increased. Furthermore, IL1RAP knockdown by lentivirus could inhibit stomach carcinoma development in vitro and in vivo through weakening tumor cell proliferation, migration, invasion, therefore reducing tumor volume, weight, and biomarker levels, and increasing apoptotic level. Finally, we found IL1RAP knockdown could increase inflammation of tumor microenvironment-related inflammatory factors of stomach carcinoma, in vitro and in vivo. Our study demonstrates that IL1RAP is possibly able to regulate inflammation and apoptosis in stomach carcinoma. Furthermore, TLR4, NF-κB, IL-1 s, IL-33, and IL-36 s maybe the downstream target factor of IL1RAP in inflammation. These results may provide a new strategy for stomach carcinoma development by regulating inflammation.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

scholarly journals Role of Cathepsin S in Periodontal Inflammation and Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
S. Memmert ◽  
A. Damanaki ◽  
A. V. B. Nogueira ◽  
S. Eick ◽  
M. Nokhbehsaim ◽  
...  
Keyword(s):  
Periodontal Diseases ◽  
Interleukin 1 ◽  
Critical Role ◽  
Gingival Tissue ◽  
Cathepsin S ◽  
Protein Levels ◽  
Periodontal Inflammation

Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.

scholarly journals The thiol redox state of lymphoid organs is modified by immunization: Role of different immune cell populations

2008 ◽  
Vol 38 (9) ◽  
pp. 2419-2425 ◽  
Author(s):  
Patrizia Castellani ◽  
Giovanna Angelini ◽  
Laura Delfino ◽  
Andrea Matucci ◽  
Anna Rubartelli
Keyword(s):  
Redox State ◽  
Immune Cell ◽  
Lymphoid Organs ◽  
Cell Populations ◽  
Thiol Redox State ◽  
Thiol Redox

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Medawar’s PostEra: Galectins Emerged as Key Players During Fetal-Maternal Glycoimmune Adaptation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ellen Menkhorst ◽  
Nandor Gabor Than ◽  
Udo Jeschke ◽  
Gabriela Barrientos ◽  
Laszlo Szereday ◽  
...  
Keyword(s):  
Immune Cell ◽  
Successful Pregnancy ◽  
Fetal Health ◽  
The Past ◽  
Mammalian Embryogenesis ◽  
Carbohydrate Ligands ◽  
Membrane Bound

Lectin-glycan interactions, in particular those mediated by the galectin family, regulate many processes required for a successful pregnancy. Over the past decades, increasing evidence gathered from in vitro and in vivo experiments indicate that members of the galectin family specifically bind to both intracellular and membrane bound carbohydrate ligands regulating angiogenesis, immune-cell adaptations required to tolerate the fetal semi-allograft and mammalian embryogenesis. Therefore, galectins play important roles in fetal development and placentation contributing to maternal and fetal health. This review discusses the expression and role of galectins during the course of pregnancy, with an emphasis on maternal immune adaptions and galectin-glycan interactions uncovered in the recent years. In addition, we summarize the galectin fingerprints associated with pathological gestation with particular focus on preeclampsia.

Abstract 15228: Role of Sympathetic Innervation in the Pathogenesis of Abdominal Aortic Aneurysm

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Bin JIANG ◽  
Yugang Liu ◽  
Guillermo A Ameer
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Sympathetic Innervation ◽  
Nerve Fibers ◽  
Elastic Fibers ◽  
Surgical Removal ◽  
Infrarenal Aorta ◽  
Abdominal Aortic ◽  
Nerve Bundles

Introduction: The objective of this study is to understand the role of neurological factors, specifically those from the perivascular sympathetic nervous system (SNS), on the initiation and development of Abdominal Aortic Aneurysm (AAA). Hypothesis: We hypothesize that the formation of AAA is associated with the loss of perivascular SNS-induced vasoconstriction specific to the aneurysm region. Methods: We developed a rat Abdominal Aortic Denervation (AAD) model, where the infrarenal aorta of Spauge Dawley rats was denervated with surgical removal of nerve fibers and chemical denervation with 10% phenol ( Figure. A ). A sham control group was included where the infrarenal aorta was treated with PBS. The arteries were harvested at 1 month after the surgeries for histological assessment. Results: The denervated aortas exhibited significant thinning of the aortic wall including the media and the adventitia, compared to the sham controls ( Figure. B ). Moreover, degradation of elastin, demonstrated by the fragmentation of elastic fibers and the decreased number of lamellar units, was also observed in the dennervated aortas in comparison to the sham controls. While the control aortas were well innervated with perivascular nerve bundles adjacent to the adventitia, no nerves were found surrounding the denervated aortas, suggesting successful denervation. Conclusions: We generated an AAD model that could be used for mechanistic understanding and therapeutic development of AAA. The preliminary data suggest a direct link between the lack of aortic sympathetic innervation and AAA formation. Long-term studies are currently underway to further characterize changes in the aortic walls after sympathetic denervation. Figure. (A) Illustration of the denervated region on the rat infrarenal aorta. ( B ) Histological staining of control and denervated rat abdominal aortas at 1 month after surgery. Yellow stars: para-aortic nerve bundles. Scale bar = 200 μm.

scholarly journals Interleukin-1-induced leukocyte extravasation across rat mesenteric microvessels is mediated by platelet-activating factor

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2553-2558 ◽  
Author(s):  
S Nourshargh ◽  
SW Larkin ◽  
A Das ◽  
TJ Williams
Keyword(s):  
Vessel Wall ◽  
Interleukin 1 ◽  
Platelet Activating Factor ◽  
Micron Diameter ◽  
Paf Receptor ◽  
Leukocyte Extravasation ◽  
Mesenteric Microvessels ◽  
Adherent Leukocytes

Although our understanding of the molecular interactions that mediate the adhesion of leukocytes to venular endothelial cells has greatly expanded, very little is known about the mechanisms that mediate the passage of leukocytes across the vessel wall in vivo. The aim of the present study was to investigate the role of endogenously formed platelet-activating factor (PAF) in the process of leukocyte extravasation induced by interleukin-1 (IL-1). To determine at which stage of emigration PAF was involved, we studied the behavior of leukocytes within rat mesenteric microvessels by intravital microscopy. Rats were injected intraperitoneally with saline, recombinant rat IL-1 beta (IL-1 beta), or the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) 4 hours before the exteriorization of the mesenteric tissue. In animals treated with IL-1 beta there was a significant increase in the number of rolling and adherent leukocytes within venules (20- to 40-micron diameter) and in the number of extravasated leukocytes in the tissue. Pretreatment of rats with the PAF receptor antagonist UK-74,505 had no effect on the leukocyte responses of rolling and adhesion, but significantly inhibited the migration of the leukocytes across the vessel wall induced by IL-1 beta (76% inhibition). A structurally unrelated PAF antagonist, WEB-2170, produced the same effect (64% inhibition). However, in contrast, UK-74,505 had no effect on the leukocyte extravasation induced by FMLP, indicating selectivity for the response elicited by certain mediators. These results provide the first line of direct evidence for the involvement of endogenously formed PAF in the process of leukocyte extravasation induced by IL-1 in vivo.

scholarly journals Differential attenuation of β2 integrin–dependent and –independent neutrophil migration by Ly6G ligation

2019 ◽  
Vol 3 (3) ◽  
pp. 256-267 ◽  
Author(s):  
Pierre Cunin ◽  
Pui Y. Lee ◽  
Edy Kim ◽  
Angela B. Schmider ◽  
Nathalie Cloutier ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Neutrophil Migration ◽  
Surface Protein ◽  
Joint Inflammation ◽  
Selective Inhibition ◽  
Β2 Integrin ◽  
Β2 Integrins ◽  
Neutrophil Surface

Abstract Antibody ligation of the murine neutrophil surface protein Ly6G disrupts neutrophil migration in some contexts but not others. We tested whether this variability reflected divergent dependence of neutrophil migration on β2 integrins, adhesion molecules that interact with Ly6G at the neutrophil surface. In integrin-dependent murine arthritis, Ly6G ligation attenuated joint inflammation, even though mice lacking Ly6G altogether developed arthritis normally. By contrast, Ly6G ligation had no impact on integrin-independent neutrophil migration into inflamed lung. In peritoneum, the role of β2 integrins varied with stimulus, proving dispensable for neutrophil entry in Escherichia coli peritonitis but contributory in interleukin 1 (IL-1)–mediated sterile peritonitis. Correspondingly, Ly6G ligation attenuated only IL-1 peritonitis, disrupting the molecular association between integrins and Ly6G and inducing cell-intrinsic blockade restricted to integrin-dependent migration. Consistent with this observation, Ly6G ligation impaired integrin-mediated postadhesion strengthening for neutrophils arresting on activated cremaster endothelium in vivo. Together, these findings identify selective inhibition of integrin-mediated neutrophil emigration through Ly6G ligation, highlighting the marked site and stimulus specificity of β2 integrin dependence in neutrophil migration.

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