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HBSP improves kidney ischemia-reperfusion injury and promotes repair in properdin deficient mice via enhancing phagocytosis of tubular epithelial cells
Phagocytosis plays vital roles in injury and repair, while its regulation by properdin and innate repair receptor, a heterodimer receptor of erythropoietin receptor (EPOR)/β common receptor (βcR), in renal ischaemia-reperfusion (IR) remains unclear. Properdin, a pattern recognition molecule, facilitates phagocytosis by opsonizing damaged cells. Our previous study showed that the phagocytic function of tubular epithelial cells isolated from properdin knockout (PKO) mouse kidneys was compromised, with upregulated EPOR in IR kidneys that was further raised by PKO at repair phase. Here, helix B surface peptide (HBSP), derive...
Source: Frontiers in Immunology - May 3, 2023 Category: Allergy & Immunology Source Type: research

Properdin Deficiency Impairs Phagocytosis and Enhances Injury at Kidney Repair Phase Post Ischemia –Reperfusion
This study revealed that properdin knockout (PKO) mice exhibited greater injury in renal function and histology than wild-type (WT) mice post 72-h IR, with more apoptotic cells and macrophages in tubular lumina, increased active caspase-3 and HMGB1, but better histological structure at 24 h. Raised erythropoietin receptor by IR was furthered by PKO and positively correlated with injury and repair markers. Properdin in WT kidneys was also upregulated by IR, while H2O2-increased properdin in TECs was reduced by its small-interfering RNA (siRNA), with raised HMGB1 and apoptosis. Moreover, the phagocytic ability of WT TECs, an...
Source: Frontiers in Immunology - September 6, 2021 Category: Allergy & Immunology Source Type: research

siRNA-based identification of IBD-related targets in human monocyte-derived dendritic cells
J Immunol Methods. 2021 Apr 20:113058. doi: 10.1016/j.jim.2021.113058. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD) is thought to be caused by an aberrant host response to the commensal enteric flora in genetically susceptible individuals. Dendritic cells (DCs) play a key role in the regulation of this response as they sample gut commensals. In healthy individuals DCs actively contribute to tolerance upon recognition of these resident bacteria, whereas in individuals with IBD, DCs will initiate an inflammatory response. To mimic the disease response in vitro, human monocyte-derived DCs were matured with E...
Source: Journal of Immunological Methods - April 23, 2021 Category: Allergy & Immunology Authors: Diane Bosman-Schluep Remko de Pril Banu Verbaken Ana ïs Legent Jan Stallen Esther C de Jong Richard A J Janssen Source Type: research

Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses
This study elucidates the regulatory role of lncRNAs in monocyte to Mφ differentiation, M1/M2 dichotomy and innate immune responses. Expression profiling of eighty-eight lncRNAs in monocytes and in vitro differentiated M2 Mφ identified seventeen differentially expressed lncRNAs. Based on fold-change and significance, we selected four differentially expressed lncRNAs viz., RN7SK, GAS5, IPW, and ZFAS1 to evaluate their functional impact. LncRNA knockdown was performed on day 3 M2 Mφ and the impact on polarization was assessed on day 7 by surface marker analysis. Knockdown of RN7SK and GAS5 showed downregulation of M2 surf...
Source: Frontiers in Immunology - December 9, 2020 Category: Allergy & Immunology Source Type: research

Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
In conclusion, the method of NK cell transfection described in our present study is highly efficient, does not require expensive dedicated structures necessary for viral transduction and avoids possible risks associated with the use of viral vectors. Importantly, it may be applied to NK cells or NK-92 cell line, greatly improving their anti-tumor activity and providing a new NK cell-based platform for new protocols of adoptive immuno-therapy of cancer. Ethics Statement The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014). Author Contributions TI designed and performed res...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

NOD2 and TLR2 Signal via TBK1 and PI31 to Direct Cross-Presentation and CD8 T Cell Responses
The objective of this study was to explore the role of NOD2 and TLR2 in cross-presentation in human dendritic cells undertaking an unbiased screen. We have used a quantitative phosphoproteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by a computational analysis to identify the proteins as differentially abundant in response to NOD2 and TLR2 sensing. Validation of the phosphoproteomic analysis was performed by the detection of proteins in phosphoenriched lysates and detected by western blot. Techniques for the modulation of gene expression (shRNA and siRNA) were used to confirm the resu...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Oligomeric S100A4 Is Associated With Monocyte Innate Immune Memory and Bypass of Tolerance to Subsequent Stimulation With Lipopolysaccharides
Conclusion: Bypass of tolerance by DAMPs might be a phenomenon as important as TI, since it could explain how chronic inflammation can be maintained in spite of an environment with multiple TLR2/TLR4-ligands. In RA monocytes, a PRDM8-dependent TI mechanism could be responsible for sustained chemokine/cytokines levels. Introduction Monocytes and macrophages play a central role in the pathophysiology of inflammation. For instance, in rheumatoid arthritis (RA), activated monocytes massively infiltrate synovial tissues and produce tumor necrosis factor-α (TNFα) (1–3). Accordingly, therapies aime...
Source: Frontiers in Immunology - April 14, 2019 Category: Allergy & Immunology Source Type: research

Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

MerTK Downregulates Lipopolysaccharide-Induced Inflammation Through SOCS1 Protein but Does Not Affect Phagocytosis of Escherichia coli in Macrophages
AbstractBacterial lipopolysaccharide (LPS) induces inflammatory responsevia toll-like receptor 4 (TLR4). However, this response must be strictly regulated because unbalanced overproduction of pro-inflammatory cytokines can lead to tissue damage and even be fatal. Herein, we explore whether Mer receptor tyrosine kinase (MerTK) regulatesEscherichia coli (E.coli) LPS-induced inflammation and mediates phagocytosis ofE.coli by macrophages. The results showed that LPS activated TLR4 signaling pathway and induced MerTK pathway in RAW264.7 macrophages, including suppressor of cytokine signaling1 (SOCS1). Preincubation with MerTK-s...
Source: Inflammation - August 24, 2018 Category: Allergy & Immunology Source Type: research

Escherichia coli –derived and Staphylococcus aureus–derived extracellular vesicles induce MUC5AC expression via extracellular signal related kinase 1/2 and p38 mitogen‐activated protein kinase in human airway epithelial cells
ConclusionThe results of this study suggest that E. coli–derived and S. aureus–derived EVs induced MUC5AC expression via ERK1/2 and p38 MAPK signaling pathways in human airway epithelial cells.
Source: International Forum of Allergy and Rhinology - August 31, 2016 Category: Allergy & Immunology Authors: Chang Hoon Bae, Yoon Seok Choi, Si ‐Youn Song, Yoon‐Keun Kim, Yong‐Dae Kim Tags: ORIGINAL ARTICLE Source Type: research

Stearoyl lysophosphatidylcholine enhances the phagocytic ability of macrophages through the AMP-activated protein kinase/p38 mitogen activated protein kinase pathway.
Abstract A previous study showed that stearoyl lysophosphatidylcholine (sLPC) suppressed extracellular high mobility group box 1 translocation in macrophages stimulated with lipopolysaccharide through AMP-activated protein kinase (AMPK) activation. In the present study, we investigated whether sLPC-induced AMPK activation could enhance macrophages phagocytosis of bacteria. We found that sLPC increased phosphorylation of AMPK and acetyl-CoA carboxylase, a downstream target of AMPK, in a time- and dose-dependent manner in macrophages. Furthermore, sLPC increased the uptake of FITC-conjugated Escherichia coli by macr...
Source: International Immunopharmacology - August 8, 2016 Category: Allergy & Immunology Authors: Quan H, Hur YH, Xin C, Kim JM, Choi JI, Kim MY, Bae HB Tags: Int Immunopharmacol Source Type: research

MicroRNA target Fc receptors to regulate Ab-dependent Ag uptake in primary macrophages and dendritic cells.
In this study, we examined the role of miR-24, miR-30b and miR-142-3p in Ab Fc receptor (FcR)-mediated phagocytosis by macrophages (MΦ) and dendritic cells (DC). The expression of these miRNAs was reduced following phagocytosis of both IgG-opsonized beads and Escherichia coli, indicating their regulatory role in the process. Further, overexpression of these miRNAs impaired the uptake of IgG-coated latex beads, which corroborated the reduced secretion of the pro-inflammatory cytokines TNF-α and IL-8 and down-regulation of PKC-α, as well as superoxide-generating enzyme NADPH oxidase 2 expression level. Mechanistically, M�...
Source: Innate Immunity - July 21, 2016 Category: Allergy & Immunology Authors: Naqvi AR, Fordham JB, Nares S Tags: Innate Immun Source Type: research

The Tyrosine Kinase Pyk2 Contributes to Complement-Mediated Phagocytosis in Murine Macrophages
Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) family and is mainly expressed in neuronal and hematopoietic cells. As FAK family members are involved in signaling connections downstream of integrins, we studied the role of Pyk2 in complement-receptor 3 (CR3, also known as Mac-1, integrin αMβ2, CD11b/CD18)-mediated phagocytosis, a key process in innate immunity. Using 3 independent approaches, we observed that Pyk2 contributes to CR3-dependent phagocytosis by RAW 264.7 macrophages, but is dispensable for Fc#x03B3; receptor (Fc#x03B3;R)-mediated uptake. Reduction of Pyk2 expression lev...
Source: Journal of Innate Immunity - February 6, 2016 Category: Allergy & Immunology Source Type: research

SIGIRR participates in negative regulation of LPS response and tolerance in human bladder epithelial cells
Conclusions: In conclusion, our results suggest that SIGIRR plays an important role in the negative regulation of LPS response and tolerance in human bladder epithelial cells, possibly through its impact on TLR-mediated signaling.
Source: BMC Immunology - December 3, 2015 Category: Allergy & Immunology Authors: Dan LiXin ZhangBaiyi Chen Source Type: research

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