scholarly journals NLRC4 Mutation in flagellin-derived peptide CBLB502 ligand-binding domain reduces the inflammatory response but not radioprotective activity

2019 ◽  
Vol 60 (6) ◽  
pp. 780-785
Author(s):  
Lili Lai ◽  
Ganggang Yang ◽  
Xuelian Yao ◽  
Lei Wang ◽  
Yiqun Zhan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Nuclear Factor Kappa B ◽  
Binding Domain ◽  
Receptor Protein ◽  
Toll Like Receptor ◽  
Interleukin 18 ◽  
Radioprotective Activity ◽  
Binding Domains ◽  
Molecular Pattern ◽  
Toll Like Receptor 5

ABSTRACT Bacterial flagellin is a pathogen-associated molecular pattern recognized by surface-localized Toll-like receptor 5 (TLR5) and cytosolic NOD-like receptor protein 4 (NLRC4). CBLB502, derived from Salmonella flagellin, exhibits high radioprotective efficacy in mice and primates by regulating TLR5 and the nuclear factor kappa B (NF-κB) signaling pathway. In this study, we examined the effects of CBLB502 and mutations in its NLRC4- and TLR5-binding domains on radioprotective efficacy and the immune inflammatory response. The results showed that CBLB502 mutation with I213A in the TLR5-binding domain significantly reduced NF-κB activity and radioprotective activity, whereas CBLB502 mutation with L292A in NLRC4-binding domain did not. Additionally, CBLB502 with both mutations greatly reduced NF-κB activity and eliminated radioprotection in mice. In contrast, NLRC4-binding domain mutation reduced the secretion of inflammatory interleukin-1β and interleukin-18. CBLB502 exerts its radioprotective effects through both the TLR5 and NLRC4 pathways. Additionally, deletion in the NLRC4-binding domain did not reduce radioprotective activity but reduced the inflammatory response.

Dual Oxidase 2 is Essential for the Toll-Like Receptor 5-Mediated Inflammatory Response in Airway Mucosa

2012 ◽  
Vol 16 (1) ◽  
pp. 57-70 ◽  
Author(s):  
Jung-Hee Joo ◽  
Ji-Hwan Ryu ◽  
Chang-Hoon Kim ◽  
Hyun Jik Kim ◽  
Mi-Sun Suh ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Toll Like Receptor ◽  
Airway Mucosa ◽  
Dual Oxidase ◽  
Toll Like Receptor 5

scholarly journals Dynamics of the avian inflammatory response toSalmonellafollowing administration of the toll-like receptor 5 agonist flagellin

2007 ◽  
Vol 51 (1) ◽  
pp. 112-117 ◽  
Author(s):  
Kenneth J. Genovese ◽  
Haiqi He ◽  
Virginia K. Lowry ◽  
David J. Nisbet ◽  
Michael H. Kogut
Keyword(s):  
Inflammatory Response ◽  
Toll Like Receptor ◽  
Toll Like Receptor 5

scholarly journals Targeting NLRP3 Inflammasome in Translational Treatment of Nervous System Diseases: An Update

2021 ◽  
Vol 12 ◽  
Author(s):  
Qingying Yu ◽  
Tingting Zhao ◽  
Molin Liu ◽  
Duo Cao ◽  
Jiaxin Li ◽  
...  
Keyword(s):  
Nervous System ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Neurological Diseases ◽  
Interleukin 1Β ◽  
Receptor Protein ◽  
Inflammatory Factors ◽  
Interleukin 18 ◽  
Neuroinflammatory Response ◽  
Molecular Patterns

Neuroinflammatory response is the immune response mechanism of the innate immune system of the central nervous system. Both primary and secondary injury can activate neuroinflammatory response. Among them, the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a key role in the inflammatory response of the central system. Inflammasome is a type of pattern recognition receptor, a cytoplasmic polyprotein complex composed of members of the Nod-like receptor (NLR) family and members of the pyrin and HIN domain (PYHIN) family, which can be affected by a variety of pathogen-related molecular patterns or damage-related molecular patterns are activated. As one of the research hotspots in the field of medical research in recent years, there are increasing researches on immune function abnormalities in the onset of neurological diseases such as depression, AD, ischemic brain injury and cerebral infarction, the NLRP3 inflammasome causes the activated caspase-1 to cleave pre-interleukin-1β and pre-interleukin-18 into mature interleukin-1β and interleukin-18, in turn, a large number of inflammatory factors are produced, which participate in the occurrence and development of the above-mentioned diseases. Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response, promote the survival of nerve cells, and achieve neuroprotective effects. This article reviews NLRP3 inflammasome’s role in neurological diseases and related regulatory mechanisms, which providing references for future research in this field.

scholarly journals Flagellin-independent effects of a Toll-like receptor 5 polymorphism in the inflammatory response to Burkholderia pseudomallei

2019 ◽  
Vol 13 (5) ◽  
pp. e0007354 ◽  
Author(s):  
Amy K. Dickey ◽  
Narisara Chantratita ◽  
Sarunporn Tandhavanant ◽  
Deirdre Ducken ◽  
Lara Lovelace-Macon ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Burkholderia Pseudomallei ◽  
Toll Like Receptor ◽  
Independent Effects ◽  
Toll Like Receptor 5

Black raspberry anthocyanins protect BV2 microglia from LPS-induced inflammation through down-regulating NOX2/TXNIP/NLRP3 signaling

2021 ◽  
pp. 1-15
Author(s):  
Teng Mu ◽  
Yang Guan ◽  
Tianqiao Chen ◽  
Shuning Wang ◽  
Mei Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Receptor Protein ◽  
Black Raspberry ◽  
Interleukin 18 ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Immunological Mechanisms ◽  
Signaling Axis ◽  
Bv2 Microglia ◽  
Excessive Activation

BACKGROUND: Increasing evidence has established neuroinflammation as the hallmark of neurodegenerative disorders such as Alzheimer’s disease (AD). However, despite the underlying immunological mechanisms are far from being understood, the involvement of excessive activation of microglia is attracting more and more attention. OBJECTIVE: In the present study, we investigated the protective effect of black raspberry (BRB) anthocyanins on LPS-induced neuroinflammation in BV2 microglia. METHODS: LPS-induced mouse BV2 microglia were treated with black raspberry anthocyanins and the levels of NO, ROS, IL-1β and IL-18 produced by the cells were measured to determine the extent of oxidative stress and inflammatory response. RESULTS: The results showed that BRB anthocyanins reduced the production of ROS in LPS-induced BV2 microglia by down-regulating the level of NOX2 and its downstream factors, including thioredoxin-interacting protein (TXNIP) and NOD-like receptor protein 3 (NLRP3) inflammasome. Furthermore, BRB anthocyanins inhibited the secretion of Interleukin-18 (IL-18) and Interleukin-1β (IL-1β), eventually attenuating the LPS-induced inflammatory response of BV2 microglia. CONCLUSIONS: BRB anthocyanins might play an important neuroprotective role in inflammation-related neurodegenerative disease, potentially, by down-regulating the NOX2 /TXNIP/ NLRP3 signaling axis in brain microglia.

scholarly journals An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models

Science ◽  
2008 ◽  
Vol 320 (5873) ◽  
pp. 226-230 ◽  
Author(s):  
L. G. Burdelya ◽  
V. I. Krivokrysenko ◽  
T. C. Tallant ◽  
E. Strom ◽  
A. S. Gleiberman ◽  
...  
Keyword(s):  
Toll Like Receptor ◽  
Radioprotective Activity ◽  
Toll Like Receptor 5

Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver

Life Sciences ◽  
2016 ◽  
Vol 148 ◽  
pp. 247-253 ◽  
Author(s):  
Rômulo Pillon Barcelos ◽  
Guilherme Bresciani ◽  
Paula Rodriguez-Miguelez ◽  
Maria José Cuevas ◽  
Félix Alexandre Antunes Soares ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Rat Liver ◽  
Eccentric Exercise ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa ◽  
Pretreatment Effects

scholarly journals Purification, crystallization and X-ray crystallographic studies of flagellin fromPseudomonas aeruginosa

2014 ◽  
Vol 70 (2) ◽  
pp. 200-202 ◽  
Author(s):  
Wan Seok Song ◽  
Minsun Hong ◽  
Sung-il Yoon
Keyword(s):  
Significant Contribution ◽  
Protein Molecule ◽  
Bacterial Invasion ◽  
Toll Like Receptor ◽  
Bacterial Flagellum ◽  
Functional Studies ◽  
Molecular Pattern ◽  
Biophysical Studies ◽  
Activation Mechanisms ◽  
Toll Like Receptor 5

Flagellin constitutes the whip-like structure of the bacterial flagellum that is required for locomotion. Upon bacterial invasion into a host, flagellin functions as a pathogen-associated molecular pattern that is recognized by immune receptors, such as Toll-like receptor 5 (TLR5) and NAIP5/NLRC4, and activates host innate immunity against pathogens. Structural and biophysical studies of flagellins have been limited to those ofSalmonellaspecies. To better understand the functions of flagellin, it is necessary to study flagellins from other species. In this study, the overexpression, purification and crystallization ofPseudomonas aeruginosaflagellin that lacks the D0 domain (paflagellin-ΔD0) are reported.paflagellin-ΔD0 crystals diffracted to 2.15 Å resolution and belonged to space groupC2, with one protein molecule in the asymmetric unit. Future structure-based functional studies ofpaflagellin would extend the knowledge of the TLR5 or NAIP5/NLRC4 activation mechanisms of flagellin and would make a significant contribution to the design of flagellin vaccines and antiradiation therapeutics.

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