Bacterial Lipopolysaccharide Increases Interleukin-6 and Prostaglandin Release in Rat Cortical Type I Astrocytes by Different Mechanisms: Role of Anti-inflammatory Agents

1998 ◽  
Vol 250 (3) ◽  
pp. 798-804 ◽  
Author(s):  
Maurizio Grimaldi ◽  
Pierluigi Navarra ◽  
Giacomo Pozzoli ◽  
Paolo Preziosi ◽  
Gennaro Schettini
Keyword(s):  
Interleukin 6 ◽  
Bacterial Lipopolysaccharide ◽  
Type I ◽  
Prostaglandin Release ◽  
Anti Inflammatory

scholarly journals Inducible microRNA-590-5p inhibits host antiviral response by targeting the soluble interleukin-6 (IL6) receptor

2018 ◽  
Vol 293 (47) ◽  
pp. 18168-18179 ◽  
Author(s):  
Yaqin Zhou ◽  
Zhangchuan Xia ◽  
Zhikui Cheng ◽  
Gang Xu ◽  
Xiaodan Yang ◽  
...  
Keyword(s):  
Viral Infection ◽  
Interleukin 6 ◽  
Underlying Mechanism ◽  
Antiviral Response ◽  
Type I ◽  
Interleukin 6 Receptor ◽  
Important Regulator ◽  
Membrane Bound ◽  
Host Antiviral Response

MicroRNA (miR)-590-5p has been identified as an important regulator of some signaling pathways such as cell proliferation and tumorigenesis. However, little is known about its role during viral infection. Here, we report that miR-590-5p was significantly induced by various viruses and effectively potentiated virus replication in different viral infection systems. Furthermore, miR-590-5p substantially attenuated the virus-induced expression of type I and type III interferons (IFNs) and inflammatory cytokines, resulting in impaired downstream antiviral signaling. Interleukin-6 receptor (IL6R) was identified as a target of miR-590-5p. Interestingly, the role of miR-590-5p in virus-triggered signaling was abolished in IL6R knockout cells, and this could be rescued by restoring the expression of the soluble IL6R (sIL6R) but not the membrane-bound IL6R (mIL6R), suggesting that sIL6R is indispensable for miR-590-5p in modulating the host antiviral response. Furthermore, miR-590-5p down-regulated endogenous sIL6R and mIL6R expression through a translational repression mechanism. These findings thus uncover a previously uncharacterized role and the underlying mechanism of miR-590-5p in the innate immune response to viral infection.

scholarly journals Anti-inflammatory and pro-resolving role of mast cells during resolution of local inflammation.

2021 ◽  
Author(s):  
◽  
Lisa Kornstädt
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
The Body ◽  
Type I ◽  
Local Inflammation ◽  
Ontology Term ◽  
Resolution Of Inflammation ◽  
Macrophage Phagocytosis ◽  
Anti Inflammatory

Mast cells are long-lived tissue-resident leukocytes, located most abundantly in the skin and mucosal surfaces. They belong to the first line of defence of the body, protecting against invading pathogens, toxins and allergens. Their secretory granules are densely packed with a plethora of mediators, which can be released immediately upon activation of the cell. Next to their role in IgE-mediated allergic diseases and in promoting inflammation, potential anti-inflammatory functions have been assigned to mast cells, depending on the biological setting. The aim of this thesis was to contribute to a better understanding of the role of mast cells during the resolution of a local inflammation. Therefore, in a first of step a suitable model of a local inflammation had to be identified. Since comparison of the two Toll-like receptor (TLR)-agonists zymosan and lipopolysaccharide (LPS), which are most commonly used to locally induce inflammation, revealed a systemic response after LPS-injection and a local inflammation after zymosan-injection, the TLR2 agonist zymosan was chosen for the subsequent experiments. Multi epitope ligand cartography (MELC) combined with statistical neighbourhood analysis showed that mast cells are located in an anti-inflammatory microenvironment next to M2 macrophages during resolution of inflammation, while neutrophils and M1 macrophages are located in the zymosan-filled core of the inflammation. Furthermore, infiltrating neutrophils during peak inflammation and an increasing population of macrophages phagocytosing neutrophils during resolution of inflammation could be observed. MELC as well as flow cytometry analysis of mast cell-deficient mice revealed a decreased phagocytosing activity of macrophages in the absence of mast cells. As an untargeted approach to identify mast cell-derived mediators induced by zymosan, mRNA sequencing of bone marrow-derived mast cells (BMMCs) was performed. Gene ontology term analysis of the sequencing data revealed the induction of the type I interferon (IFN) pathway as the dominant response. Contradicting previous studies, I could validate the production of IFN-β by mast cells in response to zymosan and LPS in vitro. Furthermore IFN-β expression by mast cells was also detected in vivo. In accordance with previous studies regarding other cell types the release of IFN-β by mast cells depends on endosomal signaling. The potential of IFN-β to enhance the phagocytosing activity of macrophages has been demonstrated recently. Besides IFN-β, various other mediators with reported enhancing effects on macrophage phagocytosis were also induced by zymosan in BMMCs, including Interleukin (IL)-1β, IL-4, IL-13, and Prostaglandin (PG) E2. Thus, either one of these mediators alone or a combination of them could promote macrophage phagocytosis. In conclusion, I herein present mast cells as a novel source for IFN-β induced by non-viral TLR ligands and demonstrate their enhancing effect on macrophage phagocytosis, thereby contributing to the resolution of inflammation.

scholarly journals Glycosylated and unglycosylated human lactoferrins both bind iron and show identical affinities towards human lysozyme and bacterial lipopolysaccharide, but differ in their susceptibilities towards tryptic proteolysis

1995 ◽  
Vol 312 (1) ◽  
pp. 107-114 ◽  
Author(s):  
P H C van Berkel ◽  
M E J Geerts ◽  
H A van Veen ◽  
P M Kooiman ◽  
F R Pieper ◽  
...  
Keyword(s):  
Human Kidney ◽  
Exchange Chromatography ◽  
Protein Sequencing ◽  
Bacterial Lipopolysaccharide ◽  
Terminal Sequence ◽  
Human Lysozyme ◽  
Major Function ◽  
Sds Page ◽  
Anti Inflammatory

We studied the role of N-glycosylation of human lactoferrin (hLF) with respect to properties that are relevant to its antibacterial and anti-inflammatory activities. A human kidney-derived 293(S) cell line that constitutively expresses recombinant hLF (rhLF) was produced. The reactivity towards various antibodies of rhLF that had been expressed in the absence or presence of tunicamycin (which blocks N-linked glycosylation) did not differ from that of natural (human milk-derived) hLF. Cation-exchange chromatography and N-terminal protein sequencing showed identical cationic properties and an intact N-terminal sequence for rhLF and natural hLF. SDS/PAGE of rhLF expressed in the presence of tunicamycin revealed a protein with the same M(r) as that of enzymically deglycosylated natural hLF. Both glycosylated and unglycosylated rhLF appeared to be completely saturated with iron. The affinity of natural hLF, glycosylated and non-glycosylated rhLF for both human lysozyme (Kd 4.5 x 10(-8) M) and bacterial lipopolysaccharide did not differ. SDS/PAGE of hLF species subjected to trypsin indicated that unglycosylated rhLF was much more susceptible to degradation. Furthermore, this analysis suggests that N-glycosylation heterogeneity in natural hLF and rhLF resides in the C-lobe. Thus our results provide no argument for differential antibacterial and/or anti-inflammatory activity of natural and (glycosylated) rhLF and suggest that a major function of glycosylation in hLF is to protect it against proteolysis.

scholarly journals Type I interferon (IFN)-inducible Absent in Melanoma 2 proteins in neuroinflammation: implications for Alzheimer’s disease

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Divaker Choubey
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Types ◽  
Type I ◽  
Innate Immune Responses ◽  
The Central Nervous System ◽  
Anti Inflammatory ◽  
Species Specific

AbstractCumulative evidence indicates that activation of innate immune responses in the central nervous system (CNS) induces the expression of type 1 interferons (T1 IFNs), a family of cytokines. The T1 IFNs (IFN-α/β), through activation of the JAK/STAT-signaling in microglia, astrocytes, and neurons, induce the expression of IFN-inducible proteins, which mediate the pro- and anti-inflammatory functions of IFNs. Accordingly, T1 IFN-inducible Absent in Melanoma 2 proteins (murine Aim2 and human AIM2) negatively regulate the expression of TI IFNs and, upon sensing higher levels of cytosolic DNA, assemble the Aim2/AIM2 inflammasome, resulting in activation of caspase-1, pyroptosis, and the secretion of pro-inflammatory cytokines (e.g., IL-1β and IL-18). Of interest, studies have indicated a role for the Aim2/AIM2 proteins in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease (AD). The ability of Aim2/AIM2 proteins to exert pro- and anti-inflammatory effects in CNS may depend upon age, sex hormones, cell-types, and the expression of species-specific negative regulators of the Aim2/AIM2 inflammasome. Therefore, we discuss the role of Aim2/AIM2 proteins in the development of AD. An improved understanding of the role of Absent in Melanoma 2 proteins in AD could identify new approaches to treat patients.

Development of the Immune Response in Pneumonia Caused Pseudomonas aeruginosa (Part 2)

2016 ◽  
pp. 120-124
Author(s):  
Oleksandr Abaturov ◽  
Anna Nikulina
Keyword(s):  
Immune Response ◽  
Pseudomonas Aeruginosa ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Type I ◽  
Anti Inflammatory

In this paper, based on literature data analyzed key role of proinflammatory and anti-inflammatory cytokines in the development of immune response in pneumonia caused by Pseudomonas aeruginosa. Described signaling pathways that induce the production of interferons type I and III involved in the elimination of Pseudomonas aeruginosa.

scholarly journals The inflammatory signalling mediator TAK1 mediates lymphocyte recruitment to lipopolysaccharide-activated murine mesenchymal stem cells through interleukin-6

2021 ◽  
Author(s):  
Beatrice Oelze ◽  
Kirsten Elger ◽  
Patrik Schadzek ◽  
Laura Burmeister ◽  
Anika Hamm ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Interleukin 6 ◽  
Neutralizing Antibodies ◽  
Critical Role ◽  
Inflammatory Signals ◽  
Secreted Factors ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

AbstractAs a response to pro-inflammatory signals mesenchymal stem cells (MSCs) secrete agents and factors leading to lymphocyte recruitment, counteracting inflammation, and stimulating immunosuppression. On a molecular level, the signalling mediator TGF-β-activated kinase 1 (TAK1) is activated by many pro-inflammatory signals, plays a critical role in inflammation and regulates innate and adaptive immune responses as well. While the role of TAK1 as a signalling factor promoting inflammation is well documented, we also considered a role for TAK1 in anti-inflammatory actions exerted by activated MSCs. We, therefore, investigated the capacity of lipopolysaccharide (LPS)-treated murine MSCs with lentivirally modulated TAK1 expression levels to recruit lymphocytes. TAK1 downregulated by lentiviral vectors expressing TAK1 shRNA in murine MSCs interfered with the capacity of murine MSCs to chemoattract lymphocytes, indeed. Analysing a pool of 84 secreted factors we found that among 26 secreted cytokines/factors TAK1 regulated expression of one cytokine in LPS-activated murine MSCs in particular: interleukin-6 (IL-6). IL-6 in LPS-treated MSCs was responsible for lymphocyte recruitment as substantiated by neutralizing antibodies. Our studies, therefore, suggest that in LPS-treated murine MSCs the inflammatory signalling mediator TAK1 may exert anti-inflammatory properties via IL-6.

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