Abstract:
:Induction of osteopontin (OPN), a well-known pro-inflammatory molecule, has been observed in acetaminophen (APAP)-induced hepatotoxicity. However, the precise cell source for OPN induction and its role during APAP-induced hepatotoxicity has not been fully explored. By employing a hepatotoxic mouse model induced by APAP overdose, we demonstrate that both serum and hepatic OPN levels were significantly elevated in response to APAP treatment. Our in vivo and in vitro studies clearly indicated that the induced expression of hepatic OPN was mainly located in necrosis areas and produced by dying or dead hepatocytes. Functional experiments showed that OPN deficiency protected against the APAP-induced liver injury by inhibiting the toxic APAP metabolism via reducing the expression of the cytochrome P450 family 2 subfamily E member 1 (CYP2E1). Interestingly, this inhibition of CYP2E1 expression did not occur in unfasted Opn-/- mice, but was significant in fasted Opn-/- mice and maintained for 2 hours after APAP challenge in fasted Opn-/- mice. In addition, despite the early protective role of OPN deficiency on APAP-induced hepatotoxicity, OPN deficiency retarded injury resolution by sensitizing hepatocytes to apoptosis and impairing liver regeneration. Finally, we demonstrated that a siRNA-mediated transient hepatic Opn knockdown could sufficiently and significantly protect animals from APAP-induced hepatotoxicity and death. In conclusion, this study clearly defines the cell source of OPN induction in response to APAP treatment, provides a novel insight into the metabolic role of OPN to APAP overdose, and suggests an Opn-targeted therapeutic strategy for the treatment or prevention of APAP-induced hepatotoxicity.
journal_name
Cell Mol Immunoljournal_title
Cellular & molecular immunologyauthors
Wen Y,Wang C,Gu J,Yu C,Wang K,Sun X,Sun Y,Wu H,Tong Y,Xia Q,Kong Xdoi
10.1038/s41423-018-0033-zsubject
Has Abstractpub_date
2019-05-01 00:00:00pages
483-494issue
5eissn
1672-7681issn
2042-0226pii
10.1038/s41423-018-0033-zjournal_volume
16pub_type
杂志文章abstract::While there is mounting evidence that interleukin (IL)-23-IL-17 axis plays a critical role in the pathogenesis of various autoimmune diseases, much remains to be elucidated on how IL-23 is induced in the pathological processes. IL-23 is a heterodimer composed of p19 and p40, the latter being shared with IL-12. We prev...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2015.70
更新日期:2016-03-01 00:00:00
abstract::To construct cDNA library of nasopharyngeal carcinoma (NPC) and obtain the NPC associated or specific antigens from it, we used a powerful new method to identify the antigens eliciting humoral immune response, which is SEREX (serological identification of antigen by recombinant cDNA expression library). Autologous ser...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:
更新日期:2006-02-01 00:00:00
abstract::Vγ2Vδ2 T (also known as Vγ9Vδ2 T) cells exist only in primates, and in humans represent a major γδ T-cell sub-population in the total population of circulating γδ T cells. Results from recent studies suggest that while (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) phosphoantigen from Mycobacterium tuberculos...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章,评审
doi:10.1038/cmi.2012.46
更新日期:2013-01-01 00:00:00
abstract::Immunoglobulins (Igs) are known to be synthesized and secreted only by B lymphocytes. Class switch recombination (CSR) is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initiation is the germline transcription of Ig genes. Surprisingly, recent studies have demonstrated that the I...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2013.52
更新日期:2014-03-01 00:00:00
abstract::The outcome of hepatitis B viral (HBV) infection is determined by the complex interactions between replicating HBV and the immune system. While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively, the contribution of innate immune mechanisms remains to be defined. Her...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2017.43
更新日期:2017-12-01 00:00:00
abstract::It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury; however the underlying mechanisms remain unknown. In this paper, we demonstrated that primary hepatocytes from transgenic mice overexpressing hepatitis B virus X protein (HBX) were more susceptible to ethanol-...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:
更新日期:2005-02-01 00:00:00
abstract::Age-related thymic involution causes a decreased output of thymocytes from the thymus, thereby resulting in impairment of T cell-mediated immunity. While alterations in the T cell and non-haematopoietic stromal compartments have been described, the effects of thymic involution on thymic dendritic cells (DC) are not cl...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2009.114
更新日期:2010-03-01 00:00:00
abstract::Granulocyte colony-stimulating factor (GM-CSF), produced by CD4+ T cells, has recently been implicated in the pathogenesis of inflammatory diseases, such as multiple sclerosis and juvenile arthritis. However, the role of GM-CSF-producing CD4+ T cells in sepsis remains unknown. This study reports peripheral changes in ...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/s41423-018-0164-2
更新日期:2019-06-01 00:00:00
abstract::Allergen-specific immunotherapy (allergen-SIT) is a highly effective treatment for children with allergic asthma (AA), an immune-mediated chronic disease leading to bronchial muscle hypertrophy and airway obstruction in response to specific allergens. T helper cells and secreted cytokines play important roles in the p...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2017.26
更新日期:2018-11-01 00:00:00
abstract::In human adipose tissue and obesity, miR-99a expression is negatively correlated with inflammation. Therefore, the present study investigated the role of miR-99a in macrophage phenotype activation and adipose tissue inflammation. M2 BMDMs showed a significant increase in miR-99a expression when compared to the M0 and ...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/s41423-018-0038-7
更新日期:2019-05-01 00:00:00
abstract::Potential crosslinks between inflammation and leukaemia have been discussed for some time, but experimental evidence to support this dogma is scarce. In particular, it is important to understand the mechanisms responsible for potential upregulation of proto-oncogenic growth factor expressions by inflammatory mediators...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2014.113
更新日期:2016-01-01 00:00:00
abstract::Despite impressive results obtained in animal models, the clinical use of Fas ligand (FasL) as an anticancer drug is limited by severe toxicity. Systemic toxicity of death ligands may be prevented by using genes encoding membrane-bound death ligands and by targeted transgene expression through either targeted transduc...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章,收录出版
doi:10.1038/cmi.2009.38
更新日期:2009-08-01 00:00:00
abstract::B cells play an important role in the clearance of hepatitis B virus (HBV) and protection against reinfection. However, the functional characteristics of these cells that are associated with the outcome of chronic HBV infection remain unknown. We comprehensively investigated the frequency, phenotype, and function of p...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2015.25
更新日期:2015-05-01 00:00:00
abstract::Low-dose total body irradiation (LTBI) is used in the treatment of some cancers mainly for immune enhancement rather than cell killing. However, the mechanism underlying LTBI remains unknown. In this study, by analyzing the immune patterns of lymphocytes, we found that the percentage and absolute number of CD4(+)CD25(...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2009.117
更新日期:2010-03-01 00:00:00
abstract::The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia (PE), in which an imbalance between the inflammation-limiting regulatory T cells (Tregs) and the inflammation-mediating Th17 cells plays an essential role. Previously, we reported that the...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/s41423-018-0186-9
更新日期:2019-01-01 00:00:00
abstract::The T-cell-mediated immune response is implicated in many clinical hepatic injuries, such as autoimmune hepatitis and acute virus hepatitis. CD24 is widely expressed by different immune cells and plays an important role in the pathogenesis of many autoimmune diseases. However, the role of CD24 in T-cell-mediated liver...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2016.57
更新日期:2018-03-01 00:00:00
abstract::In previous research, chimerical BPI23-Fcgamma1 gene which consisted of human bactericidal/permeability increasing protein (BPI) gene of encoding the functional N terminus (amino acid residues 1 to 199) of human BPI and Fcgamma1 gene of encoding the Fc segment of human immunoglobulin G1 was successfully reconstructed ...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2008.55
更新日期:2008-12-01 00:00:00
abstract::We demonstrate that Mycobacterium tuberculosis recombinant leucine-responsive regulatory protein (rLrp) inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-6, and interleukin-12 production and blocks the nuclear translocation of subunits of the nuclear-receptor transcription fact...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2015.58
更新日期:2016-11-01 00:00:00
abstract::We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV) and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly....
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:
更新日期:2007-08-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Cellular & molecular immunology
pub_type: 已发布勘误
doi:10.1038/s41423-019-0332-z
更新日期:2020-03-01 00:00:00
abstract::The unmethylated CpG DNA can prevent spontaneous apoptosis of B cells. However, the precise mechanisms by which CpG DNA blocks apoptosis remain unclear. In this study, we showed B cell apoptosis was significantly inhibited by addition of CpG DNA. Treatment of CpG DNA could reduce the expression of caspase 3, increase ...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2009.24
更新日期:2009-06-01 00:00:00
abstract::Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual's own T cell repertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactions of a variety of related surface molecules (1). It induces regulatory immune responses that close...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章,评审
doi:
更新日期:2004-10-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is a heterogeneous disease with a poor prognosis and limited markers for predicting patient survival. Because chemokines and chemokine receptors play numerous and integral roles in HCC disease progression, the CXCR4-CXCL12-CXCR7 axis was studied in HCC patients. CXCR4 and CXCR7 expressio...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2014.102
更新日期:2015-07-01 00:00:00
abstract::Experimental autoimmune encephalomyelitis (EAE) is a good model for human multiple sclerosis (MS) research. However, there are some defects in the traditional models. Here, we improved the model by using the human myelin basic protein (MBP) as antigen. EAE was induced by immunization of female Wistar rats with human M...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract::Previously, we demonstrated that macrophages from thrombospondin 1 (TSP1)-deficient mice have a reduced inflammatory phenotype, suggesting that TSP1 plays a role in macrophage activation. In this study, we determined how TSP1 regulates macrophage function. We found that recombinant or purified platelet human TSP1 trea...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2013.32
更新日期:2013-11-01 00:00:00
abstract::Among various immunoregulatory molecules, the B7 family of immune-checkpoint receptors consists of highly valuable targets for cancer immunotherapy. Antibodies targeting two B7 family co-inhibitory receptors, CTLA-4 and PD-1, have elicited long-term clinical outcomes in previously refractory cancer types and are consi...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章,评审
doi:10.1038/cmi.2017.148
更新日期:2018-05-01 00:00:00
abstract::Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory gene family. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cell activation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/cmi.2017.16
更新日期:2018-09-01 00:00:00
abstract::The human immunodeficiency virus-1 (HIV-1) envelope protein gp120 is the major contributor to the pathogenesis of HIV-associated neurocognitive disorder (HAND). Neuroinflammation plays a pivotal role in gp120-induced neuropathology, but how gp120 triggers neuroinflammatory processes and subsequent neuronal death remai...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/s41423-019-0260-y
更新日期:2020-03-01 00:00:00
abstract::In cancer, myeloid cells have tumor-supporting roles. We reported that the protein GPNMB (glycoprotein nonmetastatic B) was profoundly upregulated in macrophages interacting with tumor cells. Here, using mouse tumor models, we show that macrophage-derived soluble GPNMB increases tumor growth and metastasis in Gpnmb-mu...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:10.1038/s41423-020-0501-0
更新日期:2020-07-29 00:00:00
abstract::Interleukin-22 (IL-22) is a recently identified T cell-derived cytokine whose biological significance remains obscure. Previously, we have shown that IL-22 plays a protective role in T cell-mediated hepatitis induced by Concanavalin A (Con A), acting as a survival factor for hepatocytes. In the present paper, we demon...
journal_title:Cellular & molecular immunology
pub_type: 杂志文章
doi:
更新日期:2004-02-01 00:00:00