6-Methylprednisolone down-regulates IRAK-M in human and murine osteoclasts and boosts bone-resorbing activity: a putative mechanism for corticoid-induced osteoporosis.

Abstract:

:Osteoclasts are large, multinucleated cells, which originate from the fusion of macrophages. They play a central role in bone development and remodeling via the resorption of bone and are thus important mediators of bone loss, which leads to osteoporosis. IL-1R-associated kinase (IRAK)-M is a pseudokinase, which acts as a negative modulator of innate immune responses mediated by TLRs and IL-1R. Recently, it has been reported that IRAK-M also participates in the control of macrophage differentiation into osteoclasts. In addition, it was shown that IRAK-M knockout mice develop a strong osteoporosis phenotype, suggesting that down-regulation of this molecule activates osteoclast-mediated bone resorption. We studied the effect of the osteoporosis-inducing glucocorticoid, 6-methylprednisolone (6-MP), on IRAK-M expression in osteoclasts. Our results showed that osteoclasts, derived from THP-1 and RAW cells as well as human blood monocytes, differentiated into osteoclasts, express high levels of IRAK-M at mRNA and protein levels. In addition, 6-MP down-regulates IRAK-M expression, which correlates with an increased activation of bone resorption. These findings suggest a mechanism of corticosteroid-induced osteoporosis and open new avenues for treating this endemic disease of Western societies.

journal_name

J Leukoc Biol

authors

Soares-Schanoski A,Gómez-Piña V,del Fresno C,Rodríguez-Rojas A,García F,Glaría A,Sánchez M,Vallejo-Cremades MT,Baos R,Fuentes-Prior P,Arnalich F,López-Collazo E

doi

10.1189/jlb.1106673

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

700-9

issue

3

eissn

0741-5400

issn

1938-3673

pii

jlb.1106673

journal_volume

82

pub_type

杂志文章
  • The functions of EZH2 in immune cells: Principles for novel immunotherapies.

    abstract::Enhancer of zeste homolog 2 (EZH2) is aberrantly expressed or mutated in multiple types of cancer cells and plays an oncogenic role in tumorigenesis and development in most cancers. Results from pilot clinical studies have implied that EZH2 inhibitors have therapeutic potential against some cancers. However, the exact...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/JLB.1RU0520-311R

    authors: Shao FF,Chen BJ,Wu GQ

    更新日期:2020-10-11 00:00:00

  • The effect of adenovirus-specific antibodies on adenoviral vector-induced, transgene product-specific T cell responses.

    abstract::In this study, we tested the effect of neutralizing Abs to different serotypes of E1-deleted Ad vectors on the immunogenicity of the homologous Ad vector or a vector derived from a heterologous serotype. Our results showed that, as expected, even low titers of passively transferred neutralizing Abs significantly reduc...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1A0813-451RR

    authors: Small JC,Haut LH,Bian A,Ertl HC

    更新日期:2014-11-01 00:00:00

  • Dual retrovirus integration tagging: identification of new signaling molecules Fiz1 and Hipk2 that are involved in the IL-7 signaling pathway in B lymphoblastic lymphomas.

    abstract::IL-7R, FLT3, and CD43 are surface antigens expressed during the transition from pro-B to pre-B cells in BM. To understand interactions between their signaling pathways, we analyzed spontaneous mouse B-LBLs with dual MLV integration into Stat5a and Fiz1 or Stat5a and Hipk2. MLV integration resulted in up-regulation of ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1109748

    authors: Tsuruyama T,Imai Y,Takeuchi H,Hiratsuka T,Maruyama Y,Kanaya K,Kaszynski R,Jin G,Okuno T,Ozeki M,Nakamura T,Takakuwa T,Manabe T,Tamaki K,Hiai H

    更新日期:2010-07-01 00:00:00

  • Proteasome-mediated regulation of interleukin-1beta turnover and export in human monocytes.

    abstract::Interleukin-1beta is a secreted protein that accumulates in the cytosol as an inactive precursor (pIL-1beta) before processing and release of biologically active protein. To understand the impact of this property on IL-1beta production, we examined the intracellular stability of pIL-1beta in lipopolysaccharide (LPS)-s...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Moors MA,Mizel SB

    更新日期:2000-07-01 00:00:00

  • CIRP increases ICAM-1+ phenotype of neutrophils exhibiting elevated iNOS and NETs in sepsis.

    abstract::Sepsis represents uncontrolled inflammation due to an infection. Cold-inducible RNA-binding protein (CIRP) is a stress-induced damage-associated molecular pattern (DAMP). A subset of neutrophils expressing ICAM-1+ neutrophils was previously shown to produce high levels of reactive oxygen species. The role of CIRP for ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/JLB.3A0817-327RR

    authors: Ode Y,Aziz M,Wang P

    更新日期:2018-04-01 00:00:00

  • New dog and new tricks: evolving roles for IL-33 in type 2 immunity.

    abstract::IL-33 is a more recently identified member of the IL-1 cytokine family, expressed in the nucleus of epithelial cells and released into the extracellular space following tissue damage. The impact of IL-33 as a regulator of the adaptive immune response has been studied extensively, with an understood role for IL-33 in t...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.3RI1214-595R

    authors: Lott JM,Sumpter TL,Turnquist HR

    更新日期:2015-06-01 00:00:00

  • Monoclonal antibody NIMP-R10 directed against the CD11b chain of the type 3 complement receptor can substitute for monoclonal antibody 5C6 to exacerbate listeriosis by preventing the focusing of myelomonocytic cells at infectious foci in the liver.

    abstract::Treatment of mice with a monoclonal antibody (mAb) designated NIMP-R10, directed against the CD11b polypeptide of the CD18/CD11b heterodimeric type 3 complement receptor (CR3), exacerbates listeriosis by preventing myelomonocytic cells from focusing at sites of infected hepatocytes in the liver. Under these conditions...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.52.1.130

    authors: Conlan JW,North RJ

    更新日期:1992-07-01 00:00:00

  • Altered dynamics and differential infection profiles of lymphoid and myeloid cell subsets during acute and chronic HIV-1 infection.

    abstract::The dynamics of immune cell populations during acute HIV-1 infection are not fully deciphered, especially for non-T cells. In this study, we tested whether specific cellular subsets of the innate arm of the immune response are affected early after HIV-1 infection. Using a cohort of HIV-1-infected individuals, we have ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0410231

    authors: Centlivre M,Legrand N,Steingrover R,van der Sluis R,Grijsen ML,Bakker M,Jurriaans S,Berkhout B,Paxton WA,Prins JM,Pollakis G

    更新日期:2011-05-01 00:00:00

  • Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.

    abstract::Protein kinase B (Akt) is known to be involved in proinflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of heme oxygenase (HO)-1. Up-regulation of HO-1 mediates potent, anti-inflammatory effects and attenuates organ injury. Although studies have shown that 17beta-estr...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0607355

    authors: Hsu JT,Kan WH,Hsieh CH,Choudhry MA,Schwacha MG,Bland KI,Chaudry IH

    更新日期:2007-10-01 00:00:00

  • IL-10 receptor dysfunction in macrophages during chronic inflammation.

    abstract::The immunosuppressive activity of interleukin-10 (IL-10) makes this cytokine a potentially important clinical tool to reduce inflammatory responses in various diseases. Its efficacy as a therapeutic modality is dependent on the responsiveness of immune cells. We report that macrophages from mice chronically infected w...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Avdiushko R,Hongo D,Lake-Bullock H,Kaplan A,Cohen D

    更新日期:2001-10-01 00:00:00

  • Parallel induction of epithelial surface-associated chemokine and proteoglycan by cellular hypoxia: implications for neutrophil activation.

    abstract::Neutrophil-induced damage to the protective epithelium has been implicated in mucosal disorders associated with hypoxia, and such damage may be initiated by epithelial-derived chemokines. Because chemokines can bind to membrane proteoglycans, we hypothesized that chemokines may associate with epithelial surfaces and a...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Furuta GT,Dzus AL,Taylor CT,Colgan SP

    更新日期:2000-08-01 00:00:00

  • PKC-ε pseudosubstrate and catalytic activity are necessary for membrane delivery during IgG-mediated phagocytosis.

    abstract::In RAW 264.7 cells, PKC-ε regulates FcγR-mediated phagocytosis. BMDM behave similarly; PKC-ε concentrates at phagosomes and internalization are reduced in PKC-ε⁻/⁻ cells. Two questions were asked: what is the role of PKC-ε? and what domains are necessary for PKC-ε concentration? Function was studied using BMDM and fru...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1212634

    authors: Wood TR,Chow RY,Hanes CM,Zhang X,Kashiwagi K,Shirai Y,Trebak M,Loegering DJ,Saito N,Lennartz MR

    更新日期:2013-07-01 00:00:00

  • Charcot-Leyden crystal protein in the degranulation and recovery of activated basophils.

    abstract::The Charcot-Leyden crystal (CLC) protein, a prominent cell constituent unique to eosinophils and basophils, possesses lysophospholipase activity. This activity and the extracellular deposition and formation of CLC in tissues and body fluids in association with eosinophils suggest an extracellular function for this pro...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.51.4.386

    authors: Golightly LM,Thomas LL,Dvorak AM,Ackerman SJ

    更新日期:1992-04-01 00:00:00

  • HMGN2: a novel antimicrobial effector molecule of human mononuclear leukocytes?

    abstract::Leukocytes are a central cellular element of innate-immune defense in mammals. In addition to the generation of toxic oxygen radicals and nitric oxide, leukocytes express and secrete a broad array of antimicrobial proteins and peptides. In the study, an antimicrobial polypeptide was isolated and purified from human pe...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0505280

    authors: Feng Y,Huang N,Wu Q,Wang B

    更新日期:2005-11-01 00:00:00

  • Role of IFN-gamma on dissociation between nitric oxide and TNF/IL-6 production by murine peritoneal cells after restimulation with bacterial lipopolysaccharide.

    abstract::Murine peritoneal exudate cells (PEC) pre-exposed to bacterial lipopolysaccharide (LPS) show augmented nitric oxide (NO) production by LPS restimulation, in contrast to LPS tolerance with reduced production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Significant amounts of interferon-gamma (IF...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.66.6.974

    authors: Tominaga K,Saito S,Matsuura M,Funatogawa K,Matsumura H,Nakano M

    更新日期:1999-12-01 00:00:00

  • Quantitation of conjugate formation between human polymorphonuclear leukocytes and antibody-coated target cells by flow cytometry: the role of Fc receptor and LFA-1 antigen.

    abstract::The specific binding of human polymorphonuclear leukocytes (PMN) to antibody-coated target cells was characterized by flow cytometry. PMN were labeled with phycoerythrin-E (PE) via a granulocyte-specific monoclonal antibody (leu-M1) and mixed with fluorescein isothiocyanate-labeled K562 tumor cells sensitized with rab...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.46.5.467

    authors: van Kessel KP,van Strijp JA,van der Tol ME,van Kats-Renaud HJ,Thijssen RM,Fluit AC,Verhoef J

    更新日期:1989-11-01 00:00:00

  • A new role for monoamine oxidases in the modulation of macrophage-inducible nitric oxide synthase gene expression.

    abstract::This report focuses on the modulatory role of endogenous H(2)O(2) on lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-induced inducible nitric oxide synthase (NOS2) gene expression in rat peritoneal macrophages. Exogenously added H(2)O(2) was initially found to inhibit the synthesis of NOS2, which prompted us to ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1003459

    authors: Vega A,Chacón P,Monteseirín J,El Bekay R,Alvarez M,Alba G,Conde J,Martín-Nieto J,Bedoya FJ,Pintado E,Sobrino F

    更新日期:2004-06-01 00:00:00

  • Colony-stimulating factors increase resistance to atypical mycobacteria in resistant mice, whereas they decrease resistance in susceptible strains of mice.

    abstract::Inbred strains of mice, notably the susceptible C57BL/6 and the resistant A/J strains of mice, were infected with a strain of Mycobacterium evium. The infection in the visceral organs of mice was then studied, and the effect of colony-stimulating factors, i.e., interleukin-3 (IL-3), granulocyte-macrophage colony-stimu...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.50.3.296

    authors: Denis M

    更新日期:1991-09-01 00:00:00

  • Loss of function in virus-specific lung effector T cells is independent of infection.

    abstract::Recently, several studies, including those with respiratory syncytial virus, mouse pneumovirus, and simian virus 5, have reported that virus-specific CD8+ effector cells entering the lung as a result of respiratory infection undergo significant loss of function. The impaired function in these cells has been proposed t...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0407215

    authors: Arimilli S,Palmer EM,Alexander-Miller MA

    更新日期:2008-03-01 00:00:00

  • Macrophage-colony stimulating factor is required for the production of neutrophil-promoting activity by mouse embryo fibroblasts deficient in G-CSF and GM-CSF.

    abstract::G-CSF and GM-CSF play important roles in regulating neutrophil production, survival, differentiation, and function. However, we have shown previously that G-CSF/GM-CSF double-deficient [knockout (KO)] mice still develop a profound neutrophilia in bone marrow and blood after infection with Candida albicans. This findin...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0107023

    authors: Zhang HH,Basu S,Wu F,Begley CG,Saris CJ,Dunn AR,Burgess AW,Walker F

    更新日期:2007-10-01 00:00:00

  • Differential expression of M-CSF, G-CSF, and GM-CSF by human monocytes.

    abstract::The colony-stimulating factors (CSF) belong to a group of proteins which regulate blood cell production. Human monocytes allowed to adhere express high levels of M-CSF transcripts and secreted protein at 24 h in the presence but not in the absence of indomethacin (Indo), an inhibitor of prostaglandin E (PGE) productio...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.47.3.275

    authors: Lee MT,Kaushansky K,Ralph P,Ladner MB

    更新日期:1990-03-01 00:00:00

  • Nerve growth factor regulates TNF-alpha production in mouse macrophages via MAP kinase activation.

    abstract::In this study, we examined the expression of nerve growth factor (NGF) and its receptors in mouse macrophages and the mechanisms involved in the effect of NGF on tumor necrosis factor (TNF)-alpha production. Macrophages expressed NGF and the NGF receptors TrkA and p75. Treatment of J744 cells or peritoneal macrophages...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Barouch R,Kazimirsky G,Appel E,Brodie C

    更新日期:2001-06-01 00:00:00

  • Phagosome dynamics during phagocytosis by neutrophils.

    abstract::The neutrophil is a key player in immunity, and its activities are essential for the resolution of infections. Neutrophil-pathogen interactions usually trigger a large arsenal of antimicrobial measures that leads to the highly efficient killing of pathogens. In neutrophils, the phagocytic process, including the format...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0810457

    authors: Nordenfelt P,Tapper H

    更新日期:2011-08-01 00:00:00

  • Antibody ligation of murine Ly-6G induces neutropenia, blood flow cessation, and death via complement-dependent and independent mechanisms.

    abstract::Ly-6G is a member of the Ly-6 family of GPI-linked proteins, which is expressed on murine neutrophils. Antibodies against Ly-6G cause neutropenia, and fatal reactions also develop if mice are primed with TNF-alpha prior to antibody treatment. We have investigated the mechanisms behind these responses to Ly-6G ligation...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0507305

    authors: Abbitt KB,Cotter MJ,Ridger VC,Crossman DC,Hellewell PG,Norman KE

    更新日期:2009-01-01 00:00:00

  • Effect of prostaglandins on complement production by tissue macrophages.

    abstract::Tissue macrophages produce several proteins of the complement system. The mechanisms that regulate this process are poorly understood. The established ability of certain prostaglandins to influence macrophage secretory activity suggests that these lipid mediators may also modulate complement production (CP). Using the...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.37.5.651

    authors: Rediske JJ,Pickering RJ

    更新日期:1985-05-01 00:00:00

  • Frontline Science: Corticotropin-releasing factor receptor subtype 1 is a critical modulator of mast cell degranulation and stress-induced pathophysiology.

    abstract::Life stress is a major risk factor in the onset and exacerbation of mast cell-associated diseases, including allergy/anaphylaxis, asthma, and irritable bowel syndrome. Although it is known that mast cells are highly activated upon stressful events, the mechanisms by which stress modulates mast cell function and diseas...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.2HI0317-088RR

    authors: Ayyadurai S,Gibson AJ,D'Costa S,Overman EL,Sommerville LJ,Poopal AC,Mackey E,Li Y,Moeser AJ

    更新日期:2017-12-01 00:00:00

  • Lessons from a double-transgenic neutrophil approach to induce antiproteinase 3 antibody-mediated vasculitis in mice.

    abstract::ANCA to either PR3 or MPO are found in patients with necrotizing vasculitis and glomerulonephritis. ANCA binding to their target antigens on neutrophils and subsequent neutrophil activation are pivotal disease mechanisms that lead to vascular inflammation and necrosis. ANCA interaction with PR3 is more complex than wi...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.5A0116-037R

    authors: Schreiber A,Eulenberg-Gustavus C,Bergmann A,Jerke U,Kettritz R

    更新日期:2016-12-01 00:00:00

  • Activation of rat macrophages by Betafectin PGG-glucan requires cross-linking of membrane receptors distinct from complement receptor three (CR3).

    abstract::PGG-glucan (Betafectin) is a soluble, highly purified yeast (1,3)-beta-glucan with broad anti-infective and immunomodulatory activities. These studies evaluated the ability of PGG-glucan to directly elicit O2- and tumor necrosis factor alpha (TNF-alpha) production by rat leukocytes in vitro. Particulate beta-glucan st...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.64.3.337

    authors: Michalek M,Melican D,Brunke-Reese D,Langevin M,Lemerise K,Galbraith W,Patchen M,Mackin W

    更新日期:1998-09-01 00:00:00

  • A dynamic network of estrogen receptors in murine lymphocytes: fine-tuning the immune response.

    abstract::The actual level of circulating estrogen (17β-estradiol, E2) has a serious impact on regulation of diverse immune cell functions, where their classical cytoplasmic receptors, ERα and ERβ, act as nuclear transcriptional regulators of multiple target genes. There is growing evidence, however, for rapid, "non-nuclear" re...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.2A0214-080RR

    authors: Schneider AE,Kárpáti E,Schuszter K,Tóth EA,Kiss E,Kulcsár M,László G,Matko J

    更新日期:2014-11-01 00:00:00

  • Interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist, and TNF alpha production in whole blood.

    abstract::The ability of an individual to mount defense responses to infection depend in part on the capacity to produce cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The specialized equipment, labor intensity, and sterile practice required for the standard in vitro evaluation of cytokine production ca...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.52.6.687

    authors: Nerad JL,Griffiths JK,Van der Meer JW,Endres S,Poutsiaka DD,Keusch GT,Bennish M,Salam MA,Dinarello CA,Cannon JG

    更新日期:1992-12-01 00:00:00