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Bioinformatic identification and experiment validation revealed ACTG1 is a promising prognostic signature and therapeutic target for sepsis
J Leukoc Biol. 2023 Jun 27:qiad072. doi: 10.1093/jleuko/qiad072. Online ahead of print.ABSTRACTIn the Intensive Care Unit (ICU), sepsis is a prevalent clinical syndrome that is the final pathway to death from most infections. Peripheral blood gene expression profiling is becoming more and more accepted as a potential diagnostic or prognostic tool. This work aimed to recognize genes related to sepsis, providing potential translational therapeutic targets. RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 20 healthy controls and 51 sepsis patients. Weighted gene co-expression network analysis (W...
Source: Journal of Leukocyte Biology - June 27, 2023 Category: Hematology Authors: Hua Yao Yue Zhou Tingting Li Yao Li Fan Li Geng Zhang Xin Fu Yan Kang Qin Wu Source Type: research

Sinomenine increases adenosine A < sub > 2A < /sub > receptor and inhibits NF- κB to inhibit arthritis in adjuvant-induced-arthritis rats and fibroblast-like synoviocytes through α7nAChR
J Leukoc Biol. 2021 Aug 23. doi: 10.1002/JLB.3MA0121-024RRRR. Online ahead of print.ABSTRACTSinomenine (SIN) is a clinical drug for treating rheumatoid arthritis (RA) in China. Our previous study found SIN inhibited inflammation via alpha7 nicotinic acetylcholine receptor (α7nAChR) in macrophages in vitro. Adenosine receptor A2A has anti-inflammatory and immunosuppressive function. However, the mechanisms of SIN acting on α7nAChR and the effect on adenosine A2A receptor (A2A R) in RA are not clear. In the present study, the effects of SIN on adjuvant-induced-arthritis (AIA) rats in vivo and on fibroblast-like synoviocyte...
Source: Journal of Leukocyte Biology - August 23, 2021 Category: Hematology Authors: Lang Yi Junyu Ke Jiayan Liu Huili Lai Yanjun Lv Chong Peng Yingkun Zhi Qun Du Liang Liu Peixun Wang Hua Zhou Yan Dong Source Type: research

Expression of inducible NOS is indispensable for the antiproliferative and proapoptotic effect of imatinib in BCR-ABL positive cells.
Abstract Chronic myeloid leukemia (CML) is characterized by constitutive BCR-ABL kinase activity, an aggressive proliferation of immature cells, and reduced differentiation. Targeting tyrosine kinase activity of BCR-ABL with imatinib is an effective therapy for the newly diagnosed CML patients; however, 20%-30% of the patients initially treated with imatinib eventually experience treatment failure. Therefore, early identification of these patients is of high clinical relevance. In the present study, we by undertaking a direct comparison of inducible NOS (iNOS) status in neutrophils from healthy volunteers, newly d...
Source: Journal of Leukocyte Biology - February 2, 2021 Category: Hematology Authors: Singh AK, Awasthi D, Dubey M, Nagarkoti S, Chandra T, Barthwal MK, Tripathi AK, Dikshit M Tags: J Leukoc Biol Source Type: research

RNF144B inhibits LPS-induced inflammatory responses via binding TBK1.
Abstract Innate immune responses need to be precisely controlled to avoid prolonged inflammation and prevent unwanted damage to the host. Here, we report that RNF144B responded dynamically to LPS stimulation and negatively regulated LPS-induced inflammation. We found that RNF144B interacted with the scaffold/dimerization domain (SDD) of TANK binding kinase 1 (TBK1) through the in between RING (IBR) domain to inhibit its phosphorylation and K63-linked polyubiquitination, which led to TBK1 inactivation, IRF3 dephosphorylation, and IFN-β reduction. RNF144B knockdown with siRNA increased IRF3 activation and IFN-β pr...
Source: Journal of Leukocyte Biology - September 10, 2019 Category: Hematology Authors: Zhang Z, Zhang L, Wang B, Zhu X, Zhao L, Chu C, Guo Q, Wei R, Yin X, Zhang Y, Li X Tags: J Leukoc Biol Source Type: research

JAGN1 is required for fungal killing in neutrophil extracellular traps: Implications for severe congenital neutropenia.
Abstract Mutations in the gene JAGN1 were recently discovered in patients with severe congenital neutropenia (SCN). Neutrophils release neutrophil extracellular traps (NETs) consisting of decondensed chromatin decorated with various granular proteins such as neutrophil elastase and myeloperoxidase (MPO) to combat microbial infections. However, whether JAGN1 is required for the formation or function of NETs is not known. Here, we analyzed primary neutrophils from a patient with homozygous JAGN1 mutations with respect to phorbol myristate acetate (PMA)-induced NET formation. NET release was observed, but there appea...
Source: Journal of Leukocyte Biology - August 14, 2018 Category: Hematology Authors: Khandagale A, Lazzaretto B, Carlsson G, Sundin M, Shafeeq S, Römling U, Fadeel B Tags: J Leukoc Biol Source Type: research

Blockade of deubiquitinase USP7 overcomes bortezomib resistance by suppressing NF- κB signaling pathway in multiple myeloma.
Blockade of deubiquitinase USP7 overcomes bortezomib resistance by suppressing NF-κB signaling pathway in multiple myeloma. J Leukoc Biol. 2018 Jul 19;: Authors: Yao Y, Zhang Y, Shi M, Sun Y, Chen C, Niu M, Zhang Q, Zeng L, Yao R, Li H, Yang J, Li Z, Xu K Abstract The treatment of multiple myeloma (MM) with bortezomib (BTZ) is promising; however, the emergence of resistance is challenging in the clinical treatment. Thus, a novel targeted treatment or exploring the mechanism underlying BTZ resistance is an urgent requisite. The current data showed that high expression of USP7 in myeloma was a predicto...
Source: Journal of Leukocyte Biology - July 19, 2018 Category: Hematology Authors: Yao Y, Zhang Y, Shi M, Sun Y, Chen C, Niu M, Zhang Q, Zeng L, Yao R, Li H, Yang J, Li Z, Xu K Tags: J Leukoc Biol Source Type: research

Heat-shock protein-90 prolongs septic neutrophil survival by protecting c-Src kinase and caspase-8 from proteasomal degradation.
Abstract The brief lifespan of the polymorphonuclear neutrophil (PMN) is regulated through its capacity to undergo apoptosis, a constitutive process that is actively inhibited during sepsis. We sought to define the cellular mechanisms through which Heat Shock Protein 90 (Hsp90) prolongs the survival of inflammatory PMN. We evaluated Hsp90 expression and interaction with client proteins in PMNs from patients with sepsis and in healthy control PMNs treated with LPS (1 μg/mL). Hsp90 activity was inhibited pharmacologically using radicicol (Rad; 1 μM), and Hsp90 transcription was silenced in septic PMN using siRNA....
Source: Journal of Leukocyte Biology - February 2, 2018 Category: Hematology Authors: Gupta S, Lee CM, Wang JF, Parodo J, Jia SH, Hu J, Marshall JC Tags: J Leukoc Biol Source Type: research

Expression of human gene coding ROR γT receptor depends on the Sp2 transcription factor.
Expression of human gene coding RORγT receptor depends on the Sp2 transcription factor. J Leukoc Biol. 2016 Nov;100(5):1213-1223 Authors: Ratajewski M, Walczak-Drzewiecka A, Gorzkiewicz M, Sałkowska A, Dastych J Abstract Th17 cells are involved in the immune response against pathogens, autoimmunity, and tumor progression. The differentiation of human Th17 cells requires the upregulation of RORγT, which in human cells is still not well understood. We identified 2 putative binding motifs for specificity protein transcription factors from the specificity protein/Kruppel-like factor family in the promo...
Source: Journal of Leukocyte Biology - October 31, 2016 Category: Hematology Authors: Ratajewski M, Walczak-Drzewiecka A, Gorzkiewicz M, Sałkowska A, Dastych J Tags: J Leukoc Biol Source Type: research

mTOR inhibition potentiates cytotoxicity of V γ4 γδ T cells via up-regulating NKG2D and TNF-α.
mTOR inhibition potentiates cytotoxicity of Vγ4 γδ T cells via up-regulating NKG2D and TNF-α. J Leukoc Biol. 2016 Nov;100(5):1181-1189 Authors: Cao G, Wang Q, Li G, Meng Z, Liu H, Tong J, Huang W, Liu Z, Jia Y, Wei J, Chi H, Yang H, Zhao L, Wu Z, Hao J, Yin Z Abstract γδ T cells play a critical role in early anti-tumor immunity and perform cytotoxicity via NKG2D for recognition and multiple cytotoxic factors for tumor killing. Recent studies have demonstrated pivotal roles of mTOR-mediated metabolism in the maturation, differentiation, and effector function of diverse immune cells, including DCs...
Source: Journal of Leukocyte Biology - October 31, 2016 Category: Hematology Authors: Cao G, Wang Q, Li G, Meng Z, Liu H, Tong J, Huang W, Liu Z, Jia Y, Wei J, Chi H, Yang H, Zhao L, Wu Z, Hao J, Yin Z Tags: J Leukoc Biol Source Type: research

Interferon regulatory factor 4 (IRF4) controls myeloid-derived suppressor cell (MDSC) differentiation and function.
In this study, we found that IRF4 expression was remarkably suppressed during the development of MDSCs in the tumor microenvironment. Both the mRNA and protein levels of IRF4 in MDSCs were gradually reduced, depending on the development of tumors in the 4T1 model. siRNA-mediated knockdown of IRF4 in bone marrow cells promoted the differentiation of PMN-MDSCs. Similarly, IRF4 inhibition in bone marrow cells using simvastatin, which has been known to inhibit IRF4 expression, increased PMN-MDSC numbers. In contrast, IRF4 overexpression in bone marrow cells inhibited the total numbers of MDSCs, especially PMN-MDSCs. Notably, t...
Source: Journal of Leukocyte Biology - September 5, 2016 Category: Hematology Authors: Nam S, Kang K, Cha JS, Kim JW, Lee HG, Kim Y, Yang Y, Lee MS, Lim JS Tags: J Leukoc Biol Source Type: research

Irgm1 is required for the inflammatory function of M1 macrophage in early experimental autoimmune encephalomyelitis.
Abstract The classically activated (M1) macrophage has been shown to play an indispensable role in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). However, most studies focus on the effect of macrophage on CNS demyelination of EAE; whether the M1 macrophage participates in early EAE and the molecular mechanism underlying remains unclear. Here, we showed that the immunity-related GTPase family member 1 (Irgm1), also known as LRG-47, was expressed in M1 macrophages of draining lymph nodes (dLNs) from C57BL/6 mice with early EAE, and the IRGM1 heterozygote substantially r...
Source: Journal of Leukocyte Biology - July 20, 2016 Category: Hematology Authors: Xu Y, He Z, Li Z, Fang S, Zhang Y, Wan C, Ma Y, Lin P, Liu C, Wang G, Li R, Zhu J, Li Y, Mu L, Zhang Y, Wang J, Kong Q, Li H, Sun B Tags: J Leukoc Biol Source Type: research

Expression of human gene coding RORγT receptor depends on the Sp2 transcription factor.
Abstract Th17 cells are involved in the immune response against pathogens, autoimmunity, and tumor progression. The differentiation of human Th17 cells requires the upregulation of RORγT, which in human cells is still not well understood. We identified 2 putative binding motifs for specificity protein transcription factors from the specificity protein/Kruppel-like factor family in the promoter of human RORγT and investigated the involvement of specificity proteins in the transcriptional regulation of this gene. To this end, a human lymphocytic cell line and in vitro-differentiated Th17 cells were used in promote...
Source: Journal of Leukocyte Biology - June 1, 2016 Category: Hematology Authors: Ratajewski M, Walczak-Drzewiecka A, Gorzkiewicz M, Sałkowska A, Dastych J Tags: J Leukoc Biol Source Type: research

mTOR inhibition potentiates cytotoxicity of Vγ4 γδ T cells via up-regulating NKG2D and TNF-α.
Abstract γδ T cells play a critical role in early anti-tumor immunity and perform cytotoxicity via NKG2D for recognition and multiple cytotoxic factors for tumor killing. Recent studies have demonstrated pivotal roles of mTOR-mediated metabolism in the maturation, differentiation, and effector function of diverse immune cells, including DCs, NK cells, CD4(+) T cell subsets, and CD8(+) T cells, but the role of mTOR signaling in γδ T cells is barely known. Here, we showed that suppressing mTOR signaling in in vitro-expanded Vγ4 γδ T cells via the mechanistic inhibitor rapamycin enhanced their cytotoxicity aga...
Source: Journal of Leukocyte Biology - June 1, 2016 Category: Hematology Authors: Cao G, Wang Q, Li G, Meng Z, Liu H, Tong J, Huang W, Liu Z, Jia Y, Wei J, Chi H, Yang H, Zhao L, Wu Z, Hao J, Yin Z Tags: J Leukoc Biol Source Type: research

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