scholarly journals When breaks get hot: inflammatory signaling in BRCA1/2-mutant cancers

2022 ◽  
Author(s):  
Marcel A.T.M. van Vugt ◽  
Eileen E. Parkes
Keyword(s):  
Inflammatory Signaling

scholarly journals ZBP1 promotes LPS-induced cell death and IL-1β release via RHIM-mediated interactions with RIPK1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hayley I. Muendlein ◽  
Wilson M. Connolly ◽  
Zoie Magri ◽  
Irina Smirnova ◽  
Vladimir Ilyukha ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Complex Formation ◽  
Complex I ◽  
Yersinia Pseudotuberculosis ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Inflammatory Signaling ◽  
Complex Ii ◽  
Dependent Model

AbstractInflammation and cell death are closely linked arms of the host immune response to infection, which when carefully balanced ensure host survival. One example of this balance is the tightly regulated transition from TNFR1-associated pro-inflammatory complex I to pro-death complex II. By contrast, here we show that a TRIF-dependent complex containing FADD, RIPK1 and caspase-8 (that we have termed the TRIFosome) mediates cell death in response to Yersinia pseudotuberculosis and LPS. Furthermore, we show that constitutive binding between ZBP1 and RIPK1 is essential for the initiation of TRIFosome interactions, caspase-8-mediated cell death and inflammasome activation, thus positioning ZBP1 as an effector of cell death in the context of bacterial blockade of pro-inflammatory signaling. Additionally, our findings offer an alternative to the TNFR1-dependent model of complex II assembly, by demonstrating pro-death complex formation reliant on TRIF signaling.

scholarly journals Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Guo-dong Zhu ◽  
Jing Yu ◽  
Zheng-yu Sun ◽  
Yan Chen ◽  
Hong-mei Zheng ◽  
...  
Keyword(s):  
Cold Shock ◽  
Mrna Level ◽  
Critical Role ◽  
Inflammatory Signaling ◽  
Heat Stable ◽  
Genome Wide ◽  
Attractive Therapeutic Target ◽  
Heat Stable Protein ◽  
Signaling Activation ◽  
Shock Proteins

AbstractGlioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-α inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1.

Vitamin D Inhibits Adipokine Production and Inflammatory Signaling Through the Vitamin D Receptor in Human Adipocytes

Obesity ◽  
2021 ◽  
Vol 29 (3) ◽  
pp. 562-568
Author(s):  
Hataikarn Nimitphong ◽  
Weimin Guo ◽  
Michael F. Holick ◽  
Susan K. Fried ◽  
Mi‐Jeong Lee
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Human Adipocytes ◽  
Inflammatory Signaling

scholarly journals MyD88 Is Not Required for Muscle Injury-Induced Endochondral Heterotopic Ossification in a Mouse Model of Fibrodysplasia Ossificans Progressiva

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 630
Author(s):  
Huili Lyu ◽  
Cody M. Elkins ◽  
Jessica L. Pierce ◽  
C. Henrique Serezani ◽  
Daniel S. Perrien
Keyword(s):  
Heterotopic Ossification ◽  
Muscle Injury ◽  
Cell Types ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Inflammatory Signaling ◽  
Conditional Deletion ◽  
Pathway Crosstalk ◽  
Multiple Cell

Excess inflammation and canonical BMP receptor (BMPR) signaling are coinciding hallmarks of the early stages of injury-induced endochondral heterotopic ossification (EHO), especially in the rare genetic disease fibrodysplasia ossificans progressiva (FOP). Multiple inflammatory signaling pathways can synergistically enhance BMP-induced Smad1/5/8 activity in multiple cell types, suggesting the importance of pathway crosstalk in EHO and FOP. Toll-like receptors (TLRs) and IL-1 receptors mediate many of the earliest injury-induced inflammatory signals largely via MyD88-dependent pathways. Thus, the hypothesis that MyD88-dependent signaling is required for EHO was tested in vitro and in vivo using global or Pdgfrα-conditional deletion of MyD88 in FOP mice. As expected, IL-1β or LPS synergistically increased Activin A (ActA)-induced phosphorylation of Smad 1/5 in fibroadipoprogenitors (FAPs) expressing Alk2R206H. However, conditional deletion of MyD88 in Pdgfrα-positive cells of FOP mice did not significantly alter the amount of muscle injury-induced EHO. Even more surprisingly, injury-induced EHO was not significantly affected by global deletion of MyD88. These studies demonstrate that MyD88-dependent signaling is dispensable for injury-induced EHO in FOP mice.

scholarly journals Histatin-1 Attenuates LPS-Induced Inflammatory Signaling in RAW264.7 Macrophages

2021 ◽  
Vol 22 (15) ◽  
pp. 7856
Author(s):  
Sang Min Lee ◽  
Kyung-No Son ◽  
Dhara Shah ◽  
Marwan Ali ◽  
Arun Balasubramaniam ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mapk Signaling ◽  
Response To Treatment ◽  
No Production ◽  
Inflammatory Signaling ◽  
Raw264.7 Macrophages ◽  
Inflammatory Mediator Production

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.

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