Search results for: Runx1 negatively regulates inflammatory cytokine production by neutrophils in response to Toll-like receptor signaling.
#32208490 // To Up
Runx1 negatively regulates inflammatory cytokine production by neutrophils in response to Toll-like receptor signaling.
RUNX1 is frequently mutated in myeloid and lymphoid malignancies. It has been shown to negatively regulate Toll-like receptor 4 (TLR4) signaling through nuclear factor κB (NF-κB) in lung epithelial cells. Here we show that RUNX1 regulates TLR1/2 and TLR4 signaling and inflammatory cytokine production by neutrophils. Hematopoietic-specific RUNX1 loss increased the production of proinflammatory mediators, including tumor necrosis factor-α (TNF-α), by bone marrow neutrophils in response to TLR1/2 and TLR4 agonists. Hematopoietic RUNX1 loss also resulted in profound damage to the lung parenchyma following inhalation of the TLR4 ligand lipopolysaccharide (LPS). However, neutrophils with neutrophil-specific RUNX1 loss lacked the inflammatory phenotype caused by pan-hematopoietic RUNX1 loss, indicating that dysregulated TLR4 signaling is not due to loss of RUNX1 in neutrophils per se. Rather, single-cell RNA sequencing indicates the dysregulation originates in a neutrophil precursor. Enhanced inflammatory cytokine production by neutrophils following pan-hematopoietic RUNX1 loss correlated with increased degradation of the inhibitor of NF-κB signaling, and RUNX1-deficient neutrophils displayed broad transcriptional upregulation of many of the core components of the TLR4 signaling pathway. Hence, early, pan-hematopoietic RUNX1 loss de-represses an innate immune signaling transcriptional program that is maintained in terminally differentiated neutrophils, resulting in their hyperinflammatory state. We hypothesize that inflammatory cytokine production by neutrophils may contribute to leukemia associated with inherited RUNX1 mutations.Dana C Bellissimo, Chia-Hui Chen, Qin Zhu, Sumedha Bagga, Chung-Tsai Lee, Bing He, Gerald B Wertheim, Martha Jordan, Kai Tan, G Scott Worthen, D Gary Gilliland, Nancy A Speck
1202 related Products with: Runx1 negatively regulates inflammatory cytokine production by neutrophils in response to Toll-like receptor signaling.
100 100.00 ug100 96T2 Pieces/Box96T2 Pieces/Box100 1mg100 μg96T4 Membranes/BoxRelated Pathways
Contact Us:
Belgium
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45 Fax 0032 16 50 90 45
[email protected]
France
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50 Fax 01 43 25 01 60
[email protected]
Germany
GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Tel 0241 40 08 90 86 Fax 0241 55 91 05 36
[email protected]
United Kingdom
GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
[email protected]
Also in
Luxembourg +35220880274
Schweiz Züri +41435006251
Danmark +4569918806
Österreich +43720880899
Česká republika Praha +420246019719
Ireland Dublin +35316526556
Norge Oslo +4721031366
Finland Helsset +358942419041
Sverige Stockholm +46852503438
Ελλάς Αθήνα +302111768494
Magyarország Budapest +3619980547
Poland
GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
Tel 058 710 33 44
Fax 058 710 33 48
[email protected]
skype gentaurpoland
Nederland
GENTAUR Nederland BV
Kuiper 1
5521 DG Eersel Nederland
Tel 0208-080893 Fax 0497-517897
[email protected]
Italy
GENTAUR SRL
IVA IT03841300167
Piazza Giacomo Matteotti, 6, 24122 Bergamo
Tel 02 36 00 65 93 Fax 02 36 00 65 94
[email protected]
Spain
GENTAUR Spain
Tel 0911876558
[email protected]
Bulgaria
GENTAUR Bulgaria
53 Iskar Str. 1191 Kokalyane, Sofia
Sofia 1000
Tel 0035924682280
Fax 0035929830072
[email protected]