scholarly journals Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells

2021 ◽  
Author(s):  
Li-xue Wang ◽  
Chao Ren ◽  
Ren-qi Yao ◽  
Yi-nan Luo ◽  
Yue Yin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Dendritic Cells ◽  
Host Response ◽  
Cellular Response ◽  
Receptor Protein ◽  
Internal Environment ◽  
Evolutionarily Conserved ◽  
Lethal Sepsis ◽  
Life Threatening ◽  
Oligomerization Domain

AbstractSepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sestrin2 (SESN2), a highly evolutionarily conserved protein, is critically involved in the cellular response to various stresses and has been confirmed to maintain the homeostasis of the internal environment. However, the potential effects of SESN2 in regulating dendritic cells (DCs) pyroptosis in the context of sepsis and the related mechanisms are poorly characterized. In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK–ATF4–CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2 appears to be essential for inhibiting NLRP3 inflammasome hyperactivation, reducing CASP-1-dependent pyroptosis, and improving sepsis outcomes through stabilization of the ER. The present study might have important implications for exploration of novel potential therapeutic targets for the treatment of sepsis complications.

scholarly journals Helminth-Primed Dendritic Cells Alter the Host Response to Enteric Bacterial Infection

2005 ◽  
Vol 176 (1) ◽  
pp. 472-483 ◽  
Author(s):  
Chien-Chang Chen ◽  
Steve Louie ◽  
Beth A. McCormick ◽  
W. Allan Walker ◽  
Hai Ning Shi
Keyword(s):  
Dendritic Cells ◽  
Bacterial Infection ◽  
Host Response ◽  
Enteric Bacterial Infection

scholarly journals TSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress response

2015 ◽  
Vol 46 (2) ◽  
pp. 455-463 ◽  
Author(s):  
Matthew J. Elder ◽  
Steven J. Webster ◽  
David L. Williams ◽  
J. S. Hill Gaston ◽  
Jane C. Goodall
Keyword(s):  
Endoplasmic Reticulum ◽  
Dendritic Cells ◽  
Stress Response ◽  
Endoplasmic Reticulum Stress ◽  
Endoplasmic Reticulum Stress Response

Raphe Magnus Neurons Help Protect Reactions to Visceral Pain From Interruption by Cutaneous Pain

2006 ◽  
Vol 96 (6) ◽  
pp. 3423-3432 ◽  
Author(s):  
Thaddeus S. Brink ◽  
Kevin M. Hellman ◽  
Aaron M. Lambert ◽  
Peggy Mason
Keyword(s):  
Cellular Response ◽  
Receptor Agonist ◽  
Visceral Pain ◽  
Noxious Stimulus ◽  
Colorectal Distension ◽  
Cutaneous Stimulation ◽  
Cell Discharge ◽  
Raphe Magnus ◽  
Life Threatening ◽  
On And Off Cells

Suppression of reactions to one noxious stimulus by a spatially distant noxious stimulus is termed heterotopic antinociception. In lightly anesthetized rats, a noxious visceral stimulus, colorectal distension (CRD), suppressed motor withdrawals but not blood pressure or heart rate changes evoked by noxious hindpaw heat. Microinjection of muscimol, a GABAA receptor agonist, into raphe magnus (RM) reduced CRD-evoked suppression of withdrawals, evidence that RM neurons contribute to this heterotopic antinociception. To understand how brain stem neurons contribute to heterotopic antinociception, RM neurons were recorded during CRD-elicited suppression of hindpaw withdrawals. Although subsets of RM neurons that were excited (on cells) or inhibited (off cells) by noxious cutaneous stimulation were either excited or inhibited by CRD, on cells were inhibited and off cells excited by an intracerebroventricularly administered opioid, evidence that the nociception-facilitating and -inhibiting functions of on and off cells, respectively, are predicted by the cellular response to noxious cutaneous stimulation alone and not by the response to CRD. When recorded during CRD-elicited antinociception, RM cell discharge resembled the pattern observed in response to CRD stimulation alone. However, when hindpaw withdrawal suppression was incomplete, RM cell discharge resembled the pattern observed in response to heat alone. We propose that on cells excited by CRD facilitate responses to CRD itself, which in turn augments excitation of off cells that then act to suppress cutaneous nociception. RM cells may thereby contribute to the dominance of quiet recuperative reactions evoked by potentially life-threatening visceral stimuli over transient somatomotor activity elicited by less-injurious noxious cutaneous stimuli.

scholarly journals The Endoplasmic Reticulum-resident Heat Shock Protein Gp96 Activates Dendritic Cells via the Toll-like Receptor 2/4 Pathway

2002 ◽  
Vol 277 (23) ◽  
pp. 20847-20853 ◽  
Author(s):  
Ramunas M. Vabulas ◽  
Sibylla Braedel ◽  
Norbert Hilf ◽  
Harpreet Singh-Jasuja ◽  
Sylvia Herter ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Dendritic Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Toll Like Receptor ◽  
Heat Shock Protein Gp96 ◽  
Toll Like Receptor 2

scholarly journals The Role and Mechanism of Pyroptosis and Potential Therapeutic Targets in Sepsis: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangtao Zheng ◽  
Weiwei Chen ◽  
Fangchen Gong ◽  
Ying Chen ◽  
Erzhen Chen
Keyword(s):  
Immune Response ◽  
Organ Dysfunction ◽  
Host Response ◽  
Therapeutic Targets ◽  
Host Immune Response ◽  
Unique Form ◽  
Pathogen Infection ◽  
Programmed Death ◽  
Life Threatening ◽  
Future Direction

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Recently was been found that pyroptosis is a unique form of proinflammatory programmed death, that is different from apoptosis. A growing number of studies have investigated pyroptosis and its relationship with sepsis, including the mechanisms, role, and relevant targets of pyroptosis in sepsis. While moderate pyroptosis in sepsis can control pathogen infection, excessive pyroptosis can lead to a dysregulated host immune response and even organ dysfunction. This review provides an overview of the mechanisms and potential therapeutic targets underlying pyroptosis in sepsis identified in recent decades, looking forward to the future direction of treatment for sepsis.

scholarly journals Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Wang ◽  
Ni Yang ◽  
Ri Wen ◽  
Chun-Feng Liu ◽  
Tie-Ning Zhang
Keyword(s):  
Host Response ◽  
Noncoding Rna ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Specific Treatment ◽  
Kidney Injury ◽  
Biological Processes ◽  
Immune Functions ◽  
Life Threatening ◽  
Organ Dysfunctions

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is characterized by a hyperinflammatory state accompanied by immunosuppression. Long noncoding RNAs (lncRNAs) are noncoding RNAs longer than 200 nucleotides and have important roles in mediating various biological processes. Recently, lncRNAs were found to exert both promotive and inhibitory immune functions in sepsis, thus participating in sepsis regulation. Additionally, several studies have revealed that lncRNAs are involved in sepsis-induced organ dysfunctions, including cardiovascular dysfunction, acute lung injury, and acute kidney injury. Considering the lack of effective biomarkers for early identification and specific treatment for sepsis, lncRNAs may be promising biomarkers and even targets for sepsis therapies. This review systematically highlights the recent advances regarding the roles of lncRNAs in sepsis and sheds light on their use as potential biomarkers and treatment targets for sepsis.

scholarly journals Role of Endoplasmic Reticulum Stress Sensor IRE1α in Cellular Physiology, Calcium, ROS Signaling, and Metaflammation

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1160 ◽  
Author(s):  
Thoufiqul Alam Riaz ◽  
Raghu Patil Junjappa ◽  
Mallikarjun Handigund ◽  
Jannatul Ferdous ◽  
Hyung-Ryong Kim ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Stress Sensor ◽  
Cellular Physiology ◽  
Unfolded Protein ◽  
Therapeutic Benefits ◽  
Evolutionarily Conserved ◽  
Yin And Yang ◽  
Protein Response ◽  
Diabetes And Obesity

Inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) is the most prominent and evolutionarily conserved unfolded protein response (UPR) signal transducer during endoplasmic reticulum functional upset (ER stress). A IRE1α signal pathway arbitrates yin and yang of cellular fate in objectionable conditions. It plays several roles in fundamental cellular physiology as well as in several pathological conditions such as diabetes, obesity, inflammation, cancer, neurodegeneration, and in many other diseases. Thus, further understanding of its molecular structure and mechanism of action during different cell insults helps in designing and developing better therapeutic strategies for the above-mentioned chronic diseases. In this review, recent insights into structure and mechanism of activation of IRE1α along with its complex regulating network were discussed in relation to their basic cellular physiological function. Addressing different binding partners that can modulate IRE1α function, UPRosome triggers different downstream pathways depending on the cellular backdrop. Furthermore, IRE1α are in normal cell activities outside the dominion of ER stress and activities under the weather of inflammation, diabetes, and obesity-related metaflammation. Thus, IRE1 as an ER stress sensor needs to be understood from a wider perspective for comprehensive functional meaning, which facilitates us with assembling future needs and therapeutic benefits.

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