共查询到20条相似文献,搜索用时 15 毫秒
1.
Mario M. Zaiss Kendle M. Maslowski Ilaria Mosconi Nadine Guenat Benjamin J. Marsland Nicola L. Harris 《PLoS pathogens》2013,9(8)
Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β−/−), or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity. 相似文献
2.
《Cell metabolism》2019,29(6):1350-1362.e7
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3.
Joseph S. Ainscough G. Frank Gerberick Maryam Zahedi-Nejad Gloria Lopez-Castejon David Brough Ian Kimber Rebecca J. Dearman 《The Journal of biological chemistry》2014,289(51):35582-35592
IL-1α and β are key players in the innate immune system. The secretion of these cytokines by dendritic cells (DC) is integral to the development of proinflammatory responses. These cytokines are not secreted via the classical secretory pathway. Instead, 2 independent processes are required; an initial signal to induce up-regulation of the precursor pro-IL-1α and -β, and a second signal to drive cleavage and consequent secretion. Pro-IL-1α and -β are both cytosolic and thus, are potentially subject to post-translational modifications. These modifications may, in turn, have a functional outcome in the context of IL-1α and -β secretion and hence inflammation. We report here that IL-1α and -β were degraded intracellularly in murine bone marrow-derived DC and that this degradation was dependent on active cellular processes. In addition, we demonstrate that degradation was ablated when the proteasome was inhibited, whereas autophagy did not appear to play a major role. Furthermore, inhibition of the proteasome led to an accumulation of polyubiquitinated IL-1α and -β, indicating that IL-1α and -β were polyubiquitinated prior to proteasomal degradation. Finally, our investigations suggest that polyubiquitination and proteasomal degradation are not continuous processes but instead are up-regulated following DC activation. Overall, these data highlight that IL-1α and -β polyubiquitination and proteasomal degradation are central mechanisms in the regulation of intracellular IL-1 levels in DC. 相似文献
4.
Marais M Maloney SK Gray DA 《American journal of physiology. Regulatory, integrative and comparative physiology》2011,301(3):R791-R800
There is no persuasive evidence of a correlation between proinflammatory cytokines and avian fever. In this study, for the first time, we use avian cytokines to investigate a role for proinflammatory cytokines in the central component of avian fever. IL-1β and IL-6 injected intracerebroventricularly into Pekin ducks (n = 8) initiated robust fevers of equal magnitude and duration, although there was a significant difference in the latency to a febrile response. In addition, the IL-1β-induced fever could be abolished with an intracerebroventricular injection of antibodies to avian IL-6 or an oral administration of a PG synthesis inhibitor. Our findings indicate the following sequence of events within the central component of the avian febrile mechanism: IL-1β gives rise to bioactive IL-6, which stimulates an accelerated synthesis of PGs, and these PGs then adjust the sensitivity of warm-sensitive neurons in the avian brain stem to mediate fever. Yet PGE? was not upregulated in the cerebrospinal fluid of ducks made febrile with LPS. We conclude that IL-1β and IL-6 may well mediate fever by instigating an accelerated synthesis of brain-derived PG, of a class other than PGE?, or that IL-6 serves as one of the terminal mediators of the avian febrile response. 相似文献
5.
Ioanna Marinou Simon H Till David J Moore Anthony G Wilson 《Arthritis research & therapy》2008,10(4):R80
Introduction
A feature of rheumatoid arthritis (RA) is an imbalance between proinflammatory and anti-inflammatory cytokines. Several recent studies have implicated polymorphism in the IL-4 signalling pathway in the development of erosive RA. The aim of the present study was to investigate the role of polymorphism in the IL-4, IL-4Rα and IL-13 genes in RA, including an examination of epistasis. 相似文献6.
Scofield RH 《Arthritis research & therapy》2011,13(6):137
Treatment of Sjögren's syndrome is almost entirely symptomatic. A lack of true understanding of the underlying immunological pathology of the disease prevents directed therapy. Interleukin-21 (IL-21) is elevated in the serum of patients with this disease and is expressed by the lymphocytes infiltrating the salivary glands. The known functions of IL-21 in facilitating differentiation, proliferation, and survival of both B and T cells mesh well with the findings in Sjögren's syndrome. Demonstration of IL-21 as a fundamental aspect of the pathophysiology of Sjögren's syndrome could lead to the development of anti-IL-21 therapy for this disease. 相似文献
7.
Embryo implantation, endometrial stromal cell decidualization and formation of a functional placenta are critical processes in the establishment and maintenance of pregnancy. Interleukin (IL)-11 signalling is essential for adequate decidualization in the mouse uterus and IL-11 promotes decidualization in the human. IL-11 action is mediated via binding to the specific IL-11 receptor α (IL-11Rα). The present study examined immunoreactive IL-11 and IL-11Rα in cycling rhesus monkey endometrium, at implantation sites in cynomolgus and rhesus monkeys and in human first trimester decidua and defined distinct spatial and temporal patterns. In cycling rhesus monkey endometrium, IL-11 and IL-11Rα increased in both basalis and functionalis regions during the secretory compared with the proliferative phase, with changing cellular locations in luminal and glandular epithelium and stroma. The patterns were similar overall to those previously described in human endometrium. Differences were seen in immunostaining during implantation in cynomologus and rhesus monkey. In the cynomolgus, very little staining for IL-11 or IL-11Rα was seen in syncytio- and cyto-trophoblast cells in the villi between days 12 and 150 of pregnancy although there was moderate staining in cytotrophoblast in the shell between days 12 and 17 and in subpopulations of cytotrophoblast cells invading the arteries at day 17. By contrast in the rhesus monkey between days 24 and 35 of pregnancy and in human first trimester placenta, cyto- and syncytio-trophoblast in the villi but not cytotrophoblast in the shell were positively stained. The most intense staining for both IL-11 and IL-11Rα was present within the decidua in the maternal component of implantation sites in all three primates but moderate staining was also present in maternal vascular smooth muscle and glands perivascular cells and epithelial plaques. These results are consistent with a role for IL-11 both during decidualization and placentation in primates. 相似文献
8.
Giovanni Mantovani Antonio Maccio Paola Lai Massimo Ghiani Emiliano Turnu G. Sergio Del Giacco 《Cell biochemistry and biophysics》1995,27(1):1-14
The present study investigated the peripheral blood mononuclear cells (PBMC) blastic responses to PHA, PHA plus recombinant
IL-2 (rIL-2) and rIL-2 alone; the expression of membrane-bound IL-2R on PHA-stimulated PBMC; and the levels of IL-1α, IL-2,
IL-6, and sIL-2R in serum and in culture supernatants from PHA-stimulated PBMC in 17 patients with hematological malignancies
(mean age 58.5 yr, range 22–82): 6 with non-Hodgkin’s lymphoma (NHL), 4 with Hodgkin’s lymphoma (HL), 5 with Hairy cell leukemia,
1 with chronic myelogenous leukemia, and 1 with chronic lymphocytic leukemia. The patients with HL and NHL with active disease
(AD) were separated from those in clinical remission. The patients with AD were studied at diagnosis (obviously before therapy)
and the patients in clinical remission were out of therapy since at least 6 mo. The lymphocyte blastogenic response to PHA
was significantly lower in patients with HL and NHL with AD than in the control group. The response to rIL-2 alone was in
the same range in the control group and in HL and NHL AD patients. By adding rIL-2 to PHA there was an increase of the blastogenic
response of the same patients. The percentage of CD25 expressed on PHA-stimulated lymphocytes from patients with HL and NHL
AD and from normal subjects is in the same range. Serum levels of IL-2, IL-6, and sIL-2R were significantly higher in HL and
NHL AD patients than in controls as well as in all other hematological malignancies. Supernatants derived from PHA-stimulated
PBMC were assessed for the presence of cytokines and sIL-2R by ELISA. The levels of IL-2, IL-6, and sIL-2R were significantly
lower in HL and NHL AD patients than in controls as well as in all other hematological malignancies. 相似文献
9.
Rajamanickam Anuradha Parakkal Jovvian George Luke E. Hanna Vedachalam Chandrasekaran P. Paul Kumaran Thomas B. Nutman Subash Babu 《PLoS neglected tropical diseases》2014,8(1)
Background
Two different Th2 subsets have been defined recently on the basis of IL-5 expression – an IL-5+Th2 subset and an IL-5−Th2 subset in the setting of allergy. However, the role of these newly described CD4+ T cells subpopulations has not been explored in other contexts.Methods
To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5+IL-4+IL-13+ CD4+ T cells and IL-5−IL-4 IL-13+ CD4+ T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (Fo) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP).Results
INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced Fo of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the Fo of IL-5+Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4+IL-5−Th2 subpopulation and the levels of parasite antigen – specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGFβ demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased Fo of both Th2 subsets.Conclusions
Our findings suggest that both IL-5+ and IL-5−Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes. 相似文献10.
IL-1α and IL-1β recruit different myeloid cells and promote different stages of sterile inflammation
Rider P Carmi Y Guttman O Braiman A Cohen I Voronov E White MR Dinarello CA Apte RN 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(9):4835-4843
The immune system has evolved to protect the host from invading pathogens and to maintain tissue homeostasis. Although the inflammatory process involving pathogens is well documented, the intrinsic compounds that initiate sterile inflammation and how its progression is mediated are still not clear. Because tissue injury is usually associated with ischemia and the accompanied hypoxia, the microenvironment of various pathologies involves anaerobic metabolites and products of necrotic cells. In the current study, we assessed in a comparative manner the role of IL-1α and IL-1β in the initiation and propagation of sterile inflammation induced by products of hypoxic cells. We found that following hypoxia, the precursor form of IL-1α, and not IL-1β, is upregulated and subsequently released from dying cells. Using an inflammation-monitoring system consisting of Matrigel mixed with supernatants of hypoxic cells, we noted accumulation of IL-1α in the initial phase, which correlated with the infiltration of neutrophils, and the expression of IL-1β correlated with later migration of macrophages. In addition, we were able to show that IL-1 molecules from cells transfected with either precursor IL-1α or mature IL-1β can recruit neutrophils or macrophages, respectively. Taken together, these data suggest that IL-1α, released from dying cells, initiates sterile inflammation by inducing recruitment of neutrophils, whereas IL-1β promotes the recruitment and retention of macrophages. Overall, our data provide new insight into the biology of IL-1 molecules as well as on the regulation of sterile inflammation. 相似文献
11.
Eduardo R. Ropelle Marcelo B. Flores Dennys E. Cintra Guilherme Z. Rocha José R. Pauli Joseane Morari Claudio T. de Souza Juliana C. Moraes Patrícia O. Prada Dioze Guadagnini Rodrigo M. Marin Alexandre G. Oliveira Taize M. Augusto Hernandes F. Carvalho Lício A. Velloso Mario J. A. Saad José B. C. Carvalheira 《PLoS biology》2010,8(8)
Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKβ activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKβ/NF-κB activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKβ/NF-κB signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKKβ and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin. 相似文献
12.
13.
Takao Fuchigami Toshiro Kibe Hirofumi Koyama Shosei Kishida Mikio Iijima Yoshiaki Nishizawa Hiroshi Hijioka Tomomi Fujii Masahiro Ueda Norifumi Nakamura Tohru Kiyono Michiko Kishida 《Biochemical and biophysical research communications》2014
Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. 相似文献
14.
Gonzalez-Quintial R Lawson BR Scatizzi JC Craft J Kono DH Baccala R Theofilopoulos AN 《PloS one》2011,6(11):e27528
Lupus is characterized by disturbances in lymphocyte homeostasis, as demonstrated by the marked accumulation of activated/memory T cells. Here, we provide evidence that proliferation of the CD8+ precursors for the accumulating CD4–CD8– T cells in MRL-Faslpr lupus-predisposed mice is, in part, driven by commensal antigens. The ensuing lymphadenopathy is associated with increased production of IL-7 due to expansion of fibroblastic reticular cells, the primary source of this cytokine. The excess IL-7 is not, however, consumed by CD4–CD8– T cells due to permanent down-regulation of IL-7Rα (CD127), but instead supports proliferation of autoreactive T cells and progression of autoimmunity. Accordingly, IL-7R blockade reduced T cell activation and autoimmune manifestations even when applied at advanced disease stage. These findings indicate that an imbalance favoring production over consumption of IL-7 may contribute to systemic autoimmunity, and correction of this imbalance may be a novel therapeutic approach in lymphoproliferative and autoimmune syndromes. 相似文献
15.
Padró M Mejías-Luque R Cobler L Garrido M Pérez-Garay M Puig S Peracaula R de Bolós C 《Glycoconjugate journal》2011,28(2):99-110
Inflammation of stomach mucosa has been postulated as initiator of gastric carcinogenesis and the presence of pro-inflammatory
cytokines can regulate specific genes involved in this process. The cellular expression pattern of glycosyltransferases and
Lewis antigens detected in the normal mucosa changed during the neoplassic transformation. The aim of this work was to determine
the regulation of specific fucosyltransferases and sialyltransferases by IL-1β and IL-6 pro-inflammatory cytokines in MKN45
gastric cancer cells. IL-1β induced significant increases in the mRNA levels of FUT1, FUT2 and FUT4, and decreases of FUT3
and FUT5. In IL-6 treatments, enhanced FUT1 and lower FUT3 and FUT5 mRNA expression were detected. No substantial changes
were observed in the levels of ST3GalIII and ST3GalIV. The activation of FUT1, FUT2 and FUT4 by IL-1β is through the NF-κB
pathway and the down-regulation of FUT3 and FUT5 by IL-6 is through the gp130/STAT-3 pathway, since they are inhibited specifically
by panepoxydone and AG490, respectively. The levels of Lewis antigens after IL-1β or IL-6 stimulation decreased for sialyl-Lewis
x, and no significant differences were found in the rest of the Lewis antigens analyzed, as it was also observed in subcutaneous
mice tumors from MKN45 cells treated with IL-1β or IL-6. In addition, in 61 human intestinal-type gastric tumors, sialyl-Lewis
x was highly detected in samples from patients that developed metastasis. These results indicate that the expression of the
fucosyltransferases involved in the synthesis of Lewis antigens in gastric cancer cells can be specifically modulated by IL-1β
and IL-6 inflammatory cytokines. 相似文献
16.
Juan Ma Fa-Li Zhang Gan Zhou Yu-Xin Bao Yuan Shen Zhong-Ming Qian 《Neurochemical research》2018,43(8):1624-1630
A region-specific regulation of inflammation on the expression hepcidin in the brain has been demonstrated, however, it remains unknown whether there is also a cell-specific regulation of inflammation on hepcidin in the brain. Here, we investigated the effects of lipopolysaccharides (LPS) on the expression of hepcidin mRNA and also the expression of IL-6 mRNA, the phosphorylation of STAT3 and the expression of ferroportin 1 (Fpn1) and ferritin light chain (Ft-L) proteins in neurons and astrocytes obtained from wild type (IL-6+/+) and IL-6 knockout (IL-6?/?) mice. We demonstrated that the responses of the expression of hepcidin and IL-6 mRNAs, the phosphorylation of STAT3, and the expression of Fpn1 protein to LPS in IL-6+/+ astrocytes and also the responses of the expression of hepcidin mRNA, the phosphorylation of STAT3 and the expression of Fpn1 protein to IL-6 in IL-6?/? astrocytes were much stronger than those in IL-6+/+ and IL-6?/? neurons. A significant increase in Ft-L was found in LPS-treated IL-6+/+ and IL-6-treated IL-6?/? astrocytes, but not in LPS-treated IL-6+/+ and IL-6-treated IL-6?/? neurons. Our findings provide in vitro evidence for the existence of a cell-specific regulation of LPS on the expression of hepcidin and also Ft-L in the brain. 相似文献
17.
18.
Dominik K. Fritz 《Experimental cell research》2009,315(20):3486-1214
Oncostatin M (OSM), a pleiotropic cytokine and a member of the gp130/IL-6 cytokine family, has been implicated in regulation of various chronic inflammatory processes. Previous work has shown that OSM induces eosinophil accumulation in mouse lungs in vivo and stimulates the eosinophil-selective chemokine eotaxin-1 synergistically with IL-4 in vitro. To examine the role of receptor regulation by OSM in synergistic eotaxin-1 responses, we here examine the modulation of the type-II IL-4 receptor (IL-4Rα and IL-13Rα1) by OSM and other gp130/IL-6 cytokine family members using NIH3T3 fibroblasts and primary mouse lung fibroblasts. We first show that OSM with either IL-13 or IL-4 synergistically induces eotaxin-1 expression in a dose-dependent fashion. Analysis of IL-4Rα expression at the protein (Western blot and FACS) and RNA (TAQMAN) levels showed that OSM markedly elevates expression by 3 h. OSM enhanced IL-13Rα1 mRNA and induced a smaller but detectable increase in total IL-13Rα1 protein. Priming fibroblasts with OSM for 6 h markedly enhanced subsequent IL-13 and IL-4-induced eotaxin-1 responses and STAT6 tyrosine-641 phosphorylation. Regulation of IL-4Rα by OSM was sensitive to inhibition of the PI3′K pathway by LY294002. These studies provide novel mechanistic insights in OSM role in regulation of synergistic eotaxin-1 responses and IL-4Rα expression in fibroblasts. 相似文献
19.
Studies on cytokine levels in Weil's syndrome are lacking. In this study, TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels were measured in 44 serum samples of patients diagnosed with Leptospira interrogans serovar icterohaemorrhagiae infection. TNF-α levels linked with pulmonary hemorrhagic implications, while elevated sTNFR1 and IL-10 levels linked with fatal cases. IL-6 and IL-8 did not seem to affect the outcome of the disease. Immune response pattern in Weil's syndrome bears resemblance to other patterns described for hemorrhagic fevers. IL-10/TNF-α ratio is proposed as a marker for prognosis. 相似文献
20.
Lisa F. P. Ng Angela Chow Yong-Jiang Sun Dyan J. C. Kwek Poh-Lian Lim Frederico Dimatatac Lee-Ching Ng Eng-Eong Ooi Khar-Heng Choo Zhisheng Her Philippe Kourilsky Yee-Sin Leo 《PloS one》2009,4(1)