ArticleThe Journal of biological chemistry2011
A small molecule that mimics the BB-loop in the Toll interleukin-1 (IL-1) receptor domain of MyD88 attenuates staphylococcal enterotoxin B-induced pro-inflammatory cytokine production and toxicity in mice.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Trial
- Targeting Myeloid Differentiation Primary Response Protein 88 (MyD88) and Galectin-3 to Develop Broad-Spectrum Host-Mediated Therapeutics against SARS-CoV-2.International journal of molecular sciences · 2024Review
- MyD88 and beyond: a perspective on MyD88-targeted therapeutic approach for modulation of host immunity.Immunologic research · 2021Review
- Infection-induced innate antimicrobial response disorders: from signaling pathways and their modulation to selected biomarkers.Central-European journal of immunology · 2020Review
- Select targeting of intracellular Toll-interleukin-1 receptor resistance domains for protection against influenza-induced disease.Innate immunity · 2020Article
- The Initiation of Th2 Immunity Towards Food Allergens.International journal of molecular sciences · 2018Review
- Small Molecule Analogues of the parasitic worm product ES-62 interact with the TIR domain of MyD88 to inhibit pro-inflammatory signalling.Scientific reports · 2018Article
- Multi-factorial modulation of colorectal carcinoma cells motility - partial coordination by the tetraspanin Co-029/tspan8.Oncotarget · 2017Article
- Synthetic Human TLR9-LRR11 Peptide Attenuates TLR9 Signaling by Binding to and thus Decreasing Internalization of CpG Oligodeoxynucleotides.International journal of molecular sciences · 2016Article
- Simultaneous targeting of MyD88 and Nur77 as an effective approach for the treatment of inflammatory diseases.Drug design, development and therapy · 2016Article
- Discovery of small molecule inhibitors of MyD88-dependent signaling pathways using a computational screen.Scientific reports · 2015Article
- Three conserved MyD88-recruiting TLR residues exert different effects on the human TLR4 signaling pathway.Immunologic research · 2015Article
- Prevention and treatment of Staphylococcus aureus biofilms.Expert review of anti-infective therapy · 2015Review
- Current knowledge and future directions of TLR and NOD signaling in sepsis.Military Medical Research · 2015Article
- Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome.BMC immunology · 2014Article
- Crystal structures of the Toll/Interleukin-1 receptor (TIR) domains from the Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular mimicry.The Journal of biological chemistry · 2014Article
- The staphylococcal enterotoxin (SE) family: SEB and siblings.Virulence · 2013Review
- Bacterial interference with canonical NFκB signalling.Microbiology (Reading, England) · 2013Review
- Update on staphylococcal superantigen-induced signaling pathways and therapeutic interventions.Toxins · 2013Review
- A peptide antagonist of CD28 signaling attenuates toxic shock and necrotizing soft-tissue infection induced by Streptococcus pyogenes.The Journal of infectious diseases · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxic shock syndrome (TSS) is a clinical consequence of the profound amplification of host pro-inflammatory cytokine signaling that results from staphylococcal enterotoxin (SE) exposure. We recently reported that MyD88(-/-) mice were resistant to SEA or SEB toxic shock and displayed reduced levels of pro-inflammatory cytokines in their serum. Here we report that SEB stimulation of total mononuclear cells up-regulated MyD88 in monocytes and T cells. Further, MyD88 gene silencing in primary human cells using siRNA prevented SEB or SEB plus lipopolysaccharide (LPS) induction of interleukin-1β (IL-1β) transcriptional activation, suggesting that MyD88-mediated signaling is an essential component of SEB toxicity. We synthesized small molecules that mimic the conserved BB-loop in the Toll/IL-1 receptor (TIR) domain of MyD88. In primary human cells, these mimetics attenuated SEB-induced pro-inflammatory cytokine production. SEB stimulation of primary cells with mimetic affected newly synthesized MyD88 and downstream signaling components. Furthermore, LPS-induced MyD88 signaling was likewise inhibited in a cell-based reporter assay. More importantly, administration of mimetic reduced cytokine responses and increased survivability in a murine SEB challenge model. Collectively, these results suggest that MyD88 BB-loop mimetics interfere with SEB-induced pro-inflammatory signaling and toxicity, thus offering a potential approach in the therapy of toxic shock.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.