Abstract:
:Interleukin 6 (IL-6) is involved both in immune responses and in inflammation, hematopoiesis, bone metabolism and embryonic development. IL-6 plays roles in chronic inflammation (closely related to chronic inflammatory diseases, autoimmune diseases and cancer) and even in the cytokine storm of corona virus disease 2019 (COVID-19). Acute inflammation during the immune response and wound healing is a well-controlled response, whereas chronic inflammation and the cytokine storm are uncontrolled inflammatory responses. Non-immune cells and immune cells, cytokines such as IL-1β, IL-6 and tumor necrosis factor alpha (TNFα) and transcription factors nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play central roles in inflammation. Synergistic interactions between NF-κB and STAT3 induce the hyper-activation of NF-κB followed by the production of various inflammatory cytokines. Because IL-6 is a NF-κB target, simultaneous activation of NF-κB and STAT3 in non-immune cells triggers a positive feedback loop of NF-κB activation by the IL-6-STAT3 axis. This positive feedback loop is called the IL-6 amplifier (IL-6 Amp) and is a key player in the local initiation model, which states that local initiators, such as senescence, obesity, stressors, infection, injury and smoking, trigger diseases by promoting interactions between non-immune cells and immune cells. This model counters dogma that holds that autoimmunity and oncogenesis are triggered by the breakdown of tissue-specific immune tolerance and oncogenic mutations, respectively. The IL-6 Amp is activated by a variety of local initiators, demonstrating that the IL-6-STAT3 axis is a critical target for treating diseases.
journal_name
Int Immunoljournal_title
International immunologyauthors
Hirano Tdoi
10.1093/intimm/dxaa078subject
Has Abstractpub_date
2020-12-18 00:00:00eissn
0953-8178issn
1460-2377pii
6041650pub_type
杂志文章abstract::Structural and functional aspects of the accessory molecule lymphocyte function associated antigen (LFA)-3 (CD58) have been examined following the transfection of DAP.3 and P815 cells with a cDNA clone encoding the glycosyl phosphatidylinositol (GPI)-linked form of human LFA-3. Despite earlier observations that DAP.3 ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.6.673
更新日期:1992-06-01 00:00:00
abstract::Insulitis develops in non-obese diabetic (NOD) mice as a multicentric and asynchronous process. In an effort to understand how this T cell mediated process expands within each islet and propagates between the islets of the same pancreas, we have analyzed the junctional diversity of TCR V beta 6 and V beta 8.2 transcri...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.1.139
更新日期:1995-01-01 00:00:00
abstract::The T cell Ig domain and mucin domain (TIM) proteins form a conserved family of transmembrane cell-surface glycoproteins expressed by a variety of tissues. Each TIM protein contains a single V-type Ig domain, a glycosylated mucin-like domain, a transmembrane domain and a cytoplasmic domain. TIM proteins recognize a di...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm044
更新日期:2007-06-01 00:00:00
abstract::Factors responsible for the predictable generation of Th1 or Th2 immune responses to microorganisms in vivo are not well characterized, although the ability of antigen presenting cells (APC) to provide co-stimulation, the kinetics of MHC-peptide ligand generation as well as the cytokine environment are all considered ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.4.481
更新日期:1999-04-01 00:00:00
abstract::Trypanosoma cruzi, the agent of Chagas disease contains a major cysteine proteinase, cruzipain (Cz), with an unusual carboxyl-terminal extension (C-T). We have previously reported the presence of sulfate groups in the N-linked oligosaccharide chains of this domain. In order to evaluate the immune responses to sulfated...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm149
更新日期:2008-04-01 00:00:00
abstract::Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). She...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv067
更新日期:2016-04-01 00:00:00
abstract::We have examined the role in B cell activation of ornithine decarboxylase (ODC), the labile rate-limiting enzyme in the synthesis of polyamines thought to be required for S phase entry in all cells. When small resting mouse splenic B cells were stimulated with the mitogenic agents phorbol myristate acetate (PMA) plus ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.11.1777
更新日期:1994-11-01 00:00:00
abstract::1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and the vitamin D receptor (VDR) are important regulators of autoimmunity. The effect of the VDR on the ability of mice to fight a primary or secondary infection has not been determined. Young and old VDR knockout (KO) mice were able to clear both primary and secondary infe...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn129
更新日期:2009-02-01 00:00:00
abstract::Antibody to phosphatidyl choline (PtC) is produced spontaneously in mice, by approximately 2-10% of naturally occurring CD5+ (B1) B cells in the peritoneum. Much of this antibody is encoded by the VH11 gene associated with a specific V kappa 9 gene. Constraints on the size and structure of the H chain CDR3 have been d...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.11.1365
更新日期:1993-11-01 00:00:00
abstract::Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway hyperresponsiveness (AHR), airway inflammation, enhanced recovery of T(h)2 cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition and myofibroblast transformation. Here we analyze the mechanisms responsible for the chro...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh281
更新日期:2005-08-01 00:00:00
abstract::Previously we have described the role of two 14mer peptides in autoimmune uveitis, PDSAg from the retinal autoantigen S-antigen (S-Ag) and B27PD from the sequence of disease-associated HLA-B molecules, which show antigenic mimicry. The retinal peptide gave rise to severe uveitis in the Lewis rat model of experimental ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg090
更新日期:2003-08-01 00:00:00
abstract::Tissue selective traffic of lymphocytes into different lymphoid organs is mediated by adherence of blood borne lymphocytes to specialized endothelial cells lining the high endothelial venules (HEV) in lymphoid organs. Lymphocytes discriminate between HEV in peripheral lymph nodes and in mucosal lymphoid tissues by mea...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.5.443
更新日期:1993-05-01 00:00:00
abstract::The co-existence of tumor specific immunity with a progressing tumor is observed in a variety of experimental systems and remains one of the major paradoxes of tumor immunology. We now report that a human melanoma cell line (SMC) expressing MHC class II was able to induce clonal anergy in a specific, MHC-restricted CD...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.12.1501
更新日期:1993-12-01 00:00:00
abstract::In view of our recent report that T cell receptor (TCR) alpha chain restriction fragment length polymorphism (RFLP) is associated with multiple sclerosis (MS), we have assessed the possibility that HLA-DR2, HLA-DPw4, and TCR alpha chain RFLPs may interact to increase the risk of developing MS. Detection of TCR alpha c...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.2.177
更新日期:1992-02-01 00:00:00
abstract::TCR engagement in the thymus results in both survival and elimination signals for developing thymocytes. To examine whether both signals can be provided by the same cell type, we investigated the ability of a thymic epithelial cell (TEC) line 427.1, previously shown to allow positive selection in the thymus, to induce...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.2.239
更新日期:1994-02-01 00:00:00
abstract::The integrins have been grouped into three subfamilies based on the utilization of three distinct beta chain subunits, beta 1, beta 2, and beta 3. The recent discovery of beta 4 and beta 5 subunits, and the sharing of alpha subunits between beta subfamilies reflects a greater structural and functional diversity of the...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/2.11.1097
更新日期:1990-01-01 00:00:00
abstract::At least three B cell subsets, B-1a, B-1b and B-2, or conventional B cells are present in the mouse periphery. Here we demonstrate that B-1 cells spontaneously proliferate in stationary cultures of normal adherent mouse peritoneal cells. B-1 cells were characterized by morphology, immunohistochemistry and flow cytomet...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.9.1193
更新日期:2001-09-01 00:00:00
abstract::We asked herein whether functional dendritic-like cells could be generated from t(9;22) acute lymphoblastic leukemia (ALL) blasts. We first determined that the combination of interleukin (IL)-1beta, IL-3, IL-7, tumor necrosis factor-alpha, stem cell factor and CD40 ligand was optimal for generating dendritic-like cell...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh139
更新日期:2004-10-01 00:00:00
abstract::Soluble recombinant (r) P-selectin and rP-selectin immobilized on plastic surfaces were tested for their capacity to activate neutrophils to produce superoxide anion. Soluble rP-selectin was incapable of activating leukocytes, whereas immobilized rP-selectin was able to induce leukocyte activation. When neutrophils we...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.4.487
更新日期:2000-04-01 00:00:00
abstract::Human monocytes isolated from peripheral blood of healthy donors show a time-dependent differentiation into macrophages upon in vitro cultivation, closely mimicking their in vivo migration and maturation into extravascular tissues. The mediator(s) of this maturation process has not been yet defined. We investigated th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.7.1075
更新日期:1999-07-01 00:00:00
abstract::Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against vi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxp082
更新日期:2009-10-01 00:00:00
abstract::We have previously cloned the murine homolog of cDNA for the human myelomonocytic differentiation antigen, CD14. We synthesized three hydrophilic peptides derived from the predicted amino acid sequence of murine CD14 (mCD14), designated MS7.1, MS7.2, and MS7.3, respectively, and raised antisera against them. Each anti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.2.205
更新日期:1991-02-01 00:00:00
abstract::Blocking T cell co-stimulatory signals by anti-B7-1/B7-2 mAb is an attractive approach to treat autoimmune diseases. However, anti-B7-1/B7-2 mAb treatment is known to exacerbate autoimmune diseases through mechanisms not fully understood. Tumor necrosis factor alpha (TNF-alpha) and reactive oxygen species (ROS) also p...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm012
更新日期:2007-04-01 00:00:00
abstract::CT1 is a carbohydrate moiety of CD45 that is expressed on fetal thymocytes in vivo. Examination of CT1 expression on thymocyte subsets revealed that primarily pro-T cells (CD44+ CD25+) and pre-T cells (CD44- CD25+) expressed CT1. Interestingly, non-T-lineage committed lymphoid progenitors (CD44+ CD25-) lacked CT1 indi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.4.445
更新日期:1998-04-01 00:00:00
abstract::Signal transducer and activator of transcription-1 (STAT1) signaling mediate most biological functions of IFNalpha, IFNbeta and IFNgamma although recent studies indicate that IFNgamma can alter expression of several genes via a STAT1-independent pathway. STAT1 is critical for immunity against a variety of intracellula...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn119
更新日期:2009-01-01 00:00:00
abstract::In this study, we report that the release of IL-1 receptor antagonist (IL-1ra) from IL-4-stimulated neutrophils is markedly enhanced in the presence of IL-10. We also show that up-regulation of IL-1ra release by IL-10 in IL-4-stimulated neutrophils takes place through IL-1ra mRNA stabilization and enhancement of IL-1r...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxf079
更新日期:2002-10-01 00:00:00
abstract::The regulation of MHC class II expression by the class II transactivator (CIITA) is complex and differs in various cell types depending on the relative activity of three CIITA promoters. Here we show that, in plasma cell tumors, the deacetylase inhibitor trichostatin A (TSA) elicits PIII-CIITA but does not activate th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh326
更新日期:2005-11-01 00:00:00
abstract::Epitope spreading has been best characterized as an exacerbating factor in CD4(+) T cell-dependent autoimmune disease models and is believed to occur via presentation of antigens liberated by tissue destruction initiated by CD4(+) T cells specific for a primary epitope. The growing evidence that exogenous antigens can...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.5.625
更新日期:2001-05-01 00:00:00
abstract::The immunomodulator FTY720 inhibits lymph node (LN) and thymic egress, thereby constraining T cell circulation and reducing peripheral T cell numbers. Here, we analyzed in mouse models the as yet scarcely characterized impact of long-term (up to 6 months) FTY720 exposure on T cell homeostasis and possible consequences...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn023
更新日期:2008-05-01 00:00:00
abstract::M cells are responsible for uptake of mucosal antigens in Peyer's patches (PPs). Differentiation of M cells is thought to be induced by interactions between follicle-associated epithelium and PP cells; however, it remains elusive what types of immune cells function as M-cell inducers. Here, we attempted to identify th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq478
更新日期:2011-04-01 00:00:00