Abstract：
:Activation of the NF-κB pathway is causally linked to initiation and progression of diverse cancers. Therefore, IKKβ, the key regulatory kinase of the canonical NF-κB pathway, should be a logical target for cancer treatment. However, existing IKKβ inhibitors are known to induce paradoxical immune activation, which limits their clinical usefulness. Recently, we identified a quinoxaline urea analog 13-197 as a novel IKKβ inhibitor that delays tumor growth without significant adverse effects in xenograft tumor models. In the present study, we found that 13-197 had little effect on LPS-induced NF-κB target gene induction by primary mouse macrophages while maintaining considerable anti-proliferative activities. These characteristics may explain absence of inflammatory side effects in animals treated with 13-197. Our data also demonstrate that the inflammation and proliferation-related functions of IKKβ can be uncoupled, and highlight the utility of 13-197 to dissect these downstream pathways.
journal_name
Immunol Lettjournal_title
Immunology lettersauthors
Maroni D,Rana S,Mukhopadhyay C,Natarajan A,Naramura Mdoi
10.1016/j.imlet.2015.10.011subject
Has Abstractpub_date
2015-12-01 00:00:00pages
319-24issue
2eissn
0165-2478issn
1879-0542pii
S0165-2478(15)30052-3journal_volume
168pub_type
杂志文章abstract：:We have studied the mechanisms involved in the activation or suppression of the immune response by the tumor cells, which is also dependent on the site of tumor transplantation. AK-5 tumor cells when transplanted s.c. activated peritoneal macrophages through the induction of different cytokines, whereas tumor cells wh...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(02)00034-2
更新日期：2002-07-03 00:00:00
abstract：BACKGROUND:Omalizumab therapy was found to be safe and effective as an add-on therapy for patients with poorly controlled severe asthma. Although several studies over the last decade have demonstrated its efficacy in other Immunoglobulin E related diseases, its use in such conditions is off-label. OBJECTIVE:This study...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2020.08.002
更新日期：2020-11-01 00:00:00
abstract：BACKGROUND:Infantile hemangiomas (IHs) are the most common benign tumors of childhood. They are characterized by a unique clinical course with two phases, proliferation and involution, which are followed by regression. The therapy of infantile hemangiomas was revolutionized in 2008 by the introduction of propranolol, h...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2017.03.005
更新日期：2017-05-01 00:00:00
abstract：:A novel mutant strain of rats, LEC, exhibits an arrest of T-cell maturation from CD4+CD8+ to CD4+CD8- but not the CD4-CD8+ cells in the thymus. Nevertheless, CD4+T cells arise in lymph nodes of LEC rats, implying extrathymic T-cell maturation. We analyzed the variable (V) and junctional region diversity of T-cell rece...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/0165-2478(94)00254-o
更新日期：1995-03-01 00:00:00
abstract：:The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota and food antigens. Dendritic cells (DC) generate primary T-cell responses, and determine whether these responses are immunogenic or tolerogenic. The regulatory role of D...
journal_title：Immunology letters
pub_type： 杂志文章,评审
doi：10.1016/j.imlet.2013.01.007
更新日期：2013-02-01 00:00:00
abstract：:The leukocyte common antigen, CD45, is one of the major glycoproteins on cells of hemopoietic origin showing considerable heterogeneity in both structure and expression. Biochemical heterogeneity has been attributed to differences in the primary sequence and glycosylation. In this paper we report an additional basis f...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/0165-2478(94)90198-8
更新日期：1994-04-01 00:00:00
abstract：:It has been previously shown that normal human peripheral blood mononuclear cells produce a soluble factor(s) that causes selective inhibition of collagen production by cultured human diploid fibroblasts, and that stimulation of the mononuclear cells by appropriate mitogens greatly enhances its production. Because of ...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/0165-2478(85)90145-2
更新日期：1985-01-01 00:00:00
abstract：:In some animal models of organ transplantation, notably the rat, preoperative administration of donor strain blood may produce long-term allograft survival even in the absence of adjunctive immunosuppressive therapy. The ability of blood transfusion to prevent rejection is highly dependent on the strain combination an...
journal_title：Immunology letters
pub_type： 杂志文章,评审
doi：10.1016/0165-2478(91)90213-t
更新日期：1991-07-01 00:00:00
abstract：:To study the interactions between Chlamydia trachomatis (CT) and human immunodeficiency virus (HIV) infections, we examined CT serologies in sequential serum samples of male homosexuals (MHS), followed over a mean period of 4 years. Of the MHS studied, 77 were HIV(-), 18 were HIV(+) and 10 patients seroconverted durin...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/0165-2478(94)90201-1
更新日期：1994-04-01 00:00:00
abstract：:Recent data provide evidence that antigen-specific CD4+ T-cell clones or antigen-activated T-cell lines can kill antigen-presenting cells (APC). We focused our studies on monocytes acting as APC in cultures of T cells freshly isolated from peripheral blood. The presence of monocytes in culture was monitored by their a...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/0165-2478(95)00051-6
更新日期：1995-06-01 00:00:00
abstract：:We studied CD10 Ag of neutral endopeptidase (NEP) and CD13 Ag of aminopeptidase N (APN) expression on peripheral blood mononuclear cells (PBMC) as cells activation markers and for their transendothelial migration properties in three groups of MS patients (total 58); with acute exacerbation of MS (n = 18), primary prog...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(99)00176-5
更新日期：2000-02-01 00:00:00
abstract：:We describe the quantification of the absolute amounts of HLA class II mRNA and class II transactivator (CIITA) mRNA by competitive reverse transcription polymerase chain reaction in cultured synovial fibroblast-like cells (SFC) of patients with rheumatoid arthritis. High basal levels of transcription of class II mRNA...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(97)02712-0
更新日期：1997-06-01 00:00:00
abstract：:We have reported that a cell line, KML1, obtained from lymph node cells of a 16-week-old female MRL/Mp-lpr/lpr (MRL/1) mouse produces a soluble factor(s) that promotes formation of anti-single-stranded (ss) DNA antibodies by cultures of spleen cells from old MRL/l mice (greater than 16 weeks old). Detailed examination...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/0165-2478(90)90035-o
更新日期：1990-03-01 00:00:00
abstract：:Angiogenic and poorly angiogenic tumor variants were obtained by an intraperitoneal inoculation of cells from clones of polyoma-virus transformed BALB/c 3T3 cells into syngeneic mice. The angiogenic tumor cells expressed a higher tumorigenicity phenotype and a higher capacity to produce artificial pulmonary metastases...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(96)02675-2
更新日期：1996-12-01 00:00:00
abstract：:To monitor genetically-controlled cytokine-producing ability in mice in vitro, we developed a high-density cell culture system, which is preferable for inducing CD4+ T cell-dependent self-priming responses without any antigenic stimulation. When BALB/c spleen cells were cultured at high density (over 1.0 x 10(7) cells...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(99)00143-1
更新日期：1999-12-01 00:00:00
abstract：:The prevalence of asthma and allergic disease has increased in many countries and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether whole-cell pertussis vaccine (Pw) enhanced or prevented B. per...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2004.10.011
更新日期：2005-02-15 00:00:00
abstract：:The possibility of inducing immune responses to murine interleukin-4 (IL-4) and IL-13 and generating anti-cytokine monoclonal antibodies (mAbs) was studied in IL-4- and IL-13-knockout mice. The minimal doses of IL-4 or IL-13 that could induce significant anti-cytokine responses with titers of 5000-10,000 were 20 micro...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2005.08.005
更新日期：2006-02-15 00:00:00
abstract：:The role of the immunomodulator Protein A (PA) (from Staphylococcus aureus, Cowan I strain) in the control of leishmanial infection was studied in experimental animals. Treatment of Leishmania donovani infected hamsters with PA led to a moderate level of reduction of parasite load in their spleen (68%) and liver (46%)...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(98)00102-3
更新日期：1999-02-01 00:00:00
abstract：:Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifaceted hematopoietic cytokine and the culture of mouse bone marrow with GM-CSF produces a variety of myeloid cells including granulocytes, macrophages, and dendritic cells. In the present study, we cultured mouse splenocytes with GM-CSF and examined ...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2016.03.003
更新日期：2016-05-01 00:00:00
abstract：:Phagolysis of apoptotic eosinophils plays an important role in the successful resolution of asthmatic inflammation. However, little is known about underlying mechanisms. Our aim is to investigate whether annexin I is involved in the dexamethasone-mediated enhancement of phagolysis of apoptotic eosinophils by A549 cell...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2007.06.002
更新日期：2007-08-15 00:00:00
abstract：:To elucidate the role of macrophage migration inhibitory factor (MIF) in ocular inflammation, we examined the localization of MIF in the normal anterior uveal tract of rats. Immunohistochemistry using an anti-MIF antibody revealed that MIF was present in non-pigment epithelial cells of the ciliary body and the epithel...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/0165-2478(96)02600-4
更新日期：1996-10-01 00:00:00
abstract：:While the pathophysiology of burn injury is well established in young adults, the factors that contribute to pathogenesis and increased death in elderly burn patients are not defined. The purpose of this study is to determine the effects of burn injury on mesenteric lymph node (MLN) T cell responses in young and aged ...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(03)00022-1
更新日期：2003-04-03 00:00:00
abstract：:Administration of cyclosporin A (CS-A; 25 mg/kg daily) to rats from the time of immunization with ovalbumin (OVA) in complete Freund's adjuvant abolished the production of anti-OVA antibodies, including IgE. Cyclophosphamide (Cy; 150 mg/kg) given 2 days before immunization also inhibited specific antibody production b...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/0165-2478(85)90017-3
更新日期：1985-01-01 00:00:00
abstract：:Interleukin-18 (IL-18) plays a central role in the immune response by acting on Th1 cell differentiation, cell-mediated cytotoxicity and inflammation. The role of IL-18 in cancers and inflammatory diseases is discussed in the light of our investigations on IL-18 synthesis in normal colonic mucosa, colonic cancer and C...
journal_title：Immunology letters
pub_type： 杂志文章,评审
doi：10.1016/s0165-2478(00)00285-6
更新日期：2000-12-01 00:00:00
abstract：:Zipper-interacting protein kinase (ZIPK) is a widely expressed serine/threonine kinase that has been implicated in cell death and transcriptional regulation, but its mechanism of regulation remains unknown. Here, we identified threonine-265 (Thr265) in ZIPK as a major autophosphorylation site. Mutational analyses reve...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2005.10.015
更新日期：2006-03-15 00:00:00
abstract：:A fragment of non-glycosylated E2 antigen of classical swine fever virus (CSFV), lacking the trans-membrane anchor (TM-) of the native glycoprotein, was produced in recombinant Escherichia coli strain BL21(DE3) in the form of inclusion bodies. These inclusion bodies isolated from the bacteria cells were administrated ...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2003.12.001
更新日期：2004-02-15 00:00:00
abstract：:Mouse spleen cells were activated with IL2 for 4 days in the presence or absence of paraformaldehyde fixed YAC (PFY) tumor cells (spleen cell: PFY ratio 100:1). Fresh spleen cells had poor expression of Ly49A but the expression was significantly upregulated by IL2 activation. Addition of PFYs resulted in a further boo...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(01)00206-1
更新日期：2001-06-01 00:00:00
abstract：:Fc gamma receptors type IIb1 (Fc gammaRIIb1) inhibit B-cell activation when co-ligated with B-cell antigen receptors (BCR) by immune complexes. In murine B-cells the inhibition is mediated by the interaction of the phosphorylated immunoreceptor tyrosine-based inhibitory motif (P-ITIM) of Fc gammaRIIb1 with the SH2 dom...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(96)02655-7
更新日期：1996-12-01 00:00:00
abstract：:DC are unique antigen presenting cells, and their ability to induce proliferation of T cells in a mixed leukocyte reaction (MLR) assay is commonly used for the evaluation of their function. To determine the mechanisms involved in DC-induced T cell activation in a primary MLR assay, a variety of different agents were e...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/s0165-2478(01)00235-8
更新日期：2001-09-03 00:00:00
abstract：:Th1 and Th2 cytokine response has been confirmed to be correlated with the pathogenesis of HCV infection. The aim of the study is to investigate the Th1 and Th2 cytokine profiles induced by HCV alternate reading frame protein (F protein) in chronic hepatitis C patients. We assessed the immune responses specific to HCV...
journal_title：Immunology letters
pub_type： 杂志文章
doi：10.1016/j.imlet.2013.05.002
更新日期：2013-05-01 00:00:00
