Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo.
AuthorsAnk N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR,
JournalJ Virol
PubMed ID16611910
'Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as ... More
Modulation of the phosphoinositide 3-kinase pathway alters innate resistance to polymicrobial sepsis.
AuthorsWilliams DL, Li C, Ha T, Ozment-Skelton T, Kalbfleisch JH, Preiszner J, Brooks L, Breuel K, Schweitzer JB,
JournalJ Immunol
PubMed ID14688354
'We examined the effect of modulating phosphoinositide 3-kinase (PI3K) activity in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. Inhibition of PI3K activity with wortmannin increased serum cytokine levels and decreased survival time in septic mice. We have reported that an immunomodulator, glucan phosphate, induces protection in murine ... More
Depletion of autoreactive plasma cells and treatment of lupus nephritis in mice using CEP-33779, a novel, orally active, selective inhibitor of JAK2.
AuthorsLu LD, Stump KL, Wallace NH, Dobrzanski P, Serdikoff C, Gingrich DE, Dugan BJ, Angeles TS, Albom MS, Mason JL, Ator MA, Dorsey BD, Ruggeri BA, Seavey MM,
JournalJ Immunol
PubMed ID21880982
'Accumulating evidence suggests that autoreactive plasma cells play an important role in systemic lupus erythematosus (SLE). In addition, several proinflammatory cytokines promote autoreactive B cell maturation and autoantibody production. Hence, therapeutic targeting of such cytokine pathways using a selective JAK2 inhibitor, CEP-33779 (JAK2 enzyme IC(50) = 1.3 nM; JAK3 enzyme ... More
Impact of cethromycin (ABT-773) therapy on microbiological, histologic, immunologic, and respiratory indices in a murine model of Mycoplasma pneumoniae lower respiratory infection.
AuthorsRíos AM, Mejías A, Chávez-Bueno S, Fonseca-Aten M, Katz K, Hatfield J, Gómez AM, Jafri HS, McCracken GH, Ramilo O, Hardy RD
JournalAntimicrob Agents Chemother
PubMed ID15273098
'Mycoplasma pneumoniae is a major etiologic agent of acute lower respiratory infections. We evaluated the antimicrobial and immunologic effects of cethromycin (ABT-773), a ketolide antibiotic, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were inoculated intranasally once with 10(6) CFU of M. pneumoniae on ... More
Systemic inflammation after aortic cross clamping is influenced by Toll-like receptor 2 preconditioning and deficiency.
AuthorsKoch A, Pernow M, Barthuber C, Mersmann J, Zacharowski K, Grotemeyer D,
JournalJ Surg Res
PubMed ID22622111
'The perioperative morbidity and mortality of abdominal aortic aneurysm repair is linked to systemic inflammation. Important triggers of the latter are Toll-like receptors (TLRs), which play a central role in innate immunity. Ischemia/reperfusion (I/R) injury can be influenced by either TLR stimulation before I/R (preconditioning) or TLR dysfunction (deficiency or ... More
Impaired salivary gland function in NOD mice: association with changes in cytokine profile but not with histopathologic changes in the salivary gland.
AuthorsJonsson MV, Delaleu N, Brokstad KA, Berggreen E, Skarstein K
JournalArthritis Rheum
PubMed ID16802370
'To characterize the chronologic disease course and possible interrelationships between salivary gland inflammation, hyposalivation, and cytokine levels in NOD mice, a model for Sjögren''s syndrome (SS).' ... More
Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE.
AuthorsSeavey MM, Lu LD, Stump KL, Wallace NH, Ruggeri BA,
JournalInt Immunopharmacol
PubMed ID22178195
'Current therapies for late-stage systemic lupus erythematosus (SLE) are limited to cytotoxic agents. Delanzomib (CEP-18770) is an orally active, reversible P2 threonine boronic acid inhibitor of the 26S mammalian proteasome. Delanzomib was tested in a head-to-head comparison against bortezomib to protect and treat mice with fatal lupus nephritis (LN). Age ... More
Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge.
AuthorsRice PJ, Adams EL, Ozment-Skelton T, Gonzalez AJ, Goldman MP, Lockhart BE, Barker LA, Breuel KF, Deponti WK, Kalbfleisch JH, Ensley HE, Brown GD, Gordon S, Williams DL,
JournalJ Pharmacol Exp Ther
PubMed ID15976018
'Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble glucans (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred at 4 h. In contrast, laminarin and ... More
Macrophages release tumor necrosis factor alpha and interleukin-12 in response to intracellular Bacillus anthracis spores.
AuthorsPickering AK, Merkel TJ,
JournalInfect Immun
PubMed ID15102824
Herein we report that infection of a murine macrophage cell line with Bacillus anthracis results in the production of tumor necrosis factor alpha and interleukin-12 (IL-12). When infected with B. anthracis spores in combination with lipopolysaccharide, macrophages release increased amounts of IL-12. We found no evidence of inhibition of cytokine ... More
Detection of cytokine protein expression in mouse lung homogenates using suspension bead array.
AuthorsMcDuffie E, Obert L, Chupka J, Sigler R
JournalJ Inflamm (Lond)
PubMed ID17134510
The objective for this present study was to determine whether or not suspension bead array is a feasible method to detect changes in cytokine protein expression in mouse lung tissue homogenates. Here, we report on suspension bead array as a feasible method for detection of lipopolysaccharide (LPS)-evoked changes in cytokine ... More
Induction of B-cell lymphoma by UVB radiation in p53 haploinsufficient mice.
AuthorsPuebla-Osorio N, Miyahara Y, Coimbatore S, Limón-Flores AY, Kazimi N, Ullrich SE, Zhu C
JournalBMC Cancer
PubMed ID21269511
The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe ... More
Plasmin-dependent proteolysis of tissue factor pathway inhibitor in a mouse model of endotoxemia.
AuthorsLupu C, Herlea O, Tang H, Lijnen RH, Lupu F,
JournalJ Thromb Haemost
PubMed ID23106863
The development of a procoagulant state in sepsis, owing to aberrant expression of tissue factor (TF) and a sharp decrease in the level of its major inhibitor, TF pathway inhibitor (TFPI), could lead to microthrombotic organ failure. The mechanism for the decline in TFPI activity in the lung could involve ... More
Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer.
AuthorsSeavey MM, Lu LD, Stump KL, Wallace NH, Hockeimer W, O'Kane TM, Ruggeri BA, Dobrzanski P,
JournalMol Cancer Ther
PubMed ID22334590
Constitutively activated STAT3 and STAT5 are expressed in a wide variety of human malignancies including solid and hematopoietic cancers and often correlate with a poor prognosis and resistance to multiple therapies. Given the well established role of STAT3 in tumorigenesis, inhibition of Janus-activated kinase 2 (JAK2) activity might represent an ... More
Animal models of systemic lupus erythematosus (SLE) and ex vivo assay design for drug discovery.
AuthorsSeavey MM, Lu LD, Stump KL,
JournalCurr Protoc Pharmacol
PubMed ID21935901
Systemic Lupus Erythematosus (SLE) is a debilitating and often fatal autoimmune disease that involves multiple organ systems. It can develop for years before being diagnosed. Current treatments for SLE usually involve the use of cytotoxic or immunosuppressive agents that can lead to infection or cancer. The design of appropriate models ... More
Impact of influenza vaccine formulation with a detailed analysis of the cytokine response.
AuthorsSzyszko E, Brokstad K, Cox RJ, Hovden AO, Madhun A, Haaheim LR,
JournalScand J Immunol
PubMed ID17032238
Vaccination provides the most effective method of limiting the impact of influenza. Inactivated influenza vaccines are available in three formulations and more information needs to be generated on how antigen presented in different vaccine formulations influences the subsequent immune response. In the present study, we have investigated the effect of ... More
The pro-inflammatory effect of uraemia overrules the anti-atherogenic potential of immunization with oxidized LDL in apoE-/- mice.
Uraemia increases oxidative stress, plasma titres of antibodies recognizing oxidized low-density lipoprotein (oxLDL) and development of atherosclerosis. Immunization with oxLDL prevents classical, non-uraemic atherosclerosis. We have investigated whether immunization with oxLDL might also prevent uraemia-induced atherosclerosis in apolipoprotein E knockout (apoE-/-) mice. ApoE-/- mice were immunized with either native LDL ... More
Donor CD8+ T cells mediate graft-versus-leukemia activity without clinical signs of graft-versus-host disease in recipients conditioned with anti-CD3 monoclonal antibody.
AuthorsZhang C, Lou J, Li N, Todorov I, Lin CL, Cao YA, Contag CH, Kandeel F, Forman S, Zeng D,
JournalJ Immunol
PubMed ID17202345
Donor CD8(+) T cells play a critical role in mediating graft-vs-leukemia (GVL) activity, but also induce graft-vs-host disease (GVHD) in recipients conditioned with total body irradiation (TBI). In this study, we report that injections of donor C57BL/6 (H-2(b)) or FVB/N (H-2(q)) CD8(+) T with bone marrow cells induced chimerism and ... More
HIV-1-induced pulmonary oxidative and nitrosative stress: exacerbated response to endotoxin administration in HIV-1 transgenic mouse model.
AuthorsJacob BA, Porter KM, Elms SC, Cheng PY, Jones DP, Sutliff RL,
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID16728526
Human immunodeficiency virus (HIV)-1 causes lung disease by increasing the host's susceptibility to pathogens. HIV-1 also causes an increase in systemic oxidative/nitrosative stress, perhaps enhancing the deleterious effects of secondary infections. Here we examined the ability of HIV-1 proteins to increase lung oxidative/nitrosative stress after lipopolysaccharide (LPS) (endotoxin) administration in ... More
Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury.
AuthorsWillis MS, Carlson DL, Dimaio JM, White MD, White DJ, Adams GA, Horton JW, Giroir BP,
JournalAm J Physiol Heart Circ Physiol
PubMed ID15388499
We have recently demonstrated that macrophage migration inhibitory factor (MIF) is a myocardial depressant protein and that MIF mediates late, prolonged cardiac dysfunction after endotoxin challenge in mice. Because many factors, including endotoxin, have been implicated in the pathogenesis of cardiac dysfunction after burn injury, we tested the hypothesis that ... More
Cytokine response to infection with Bacillus anthracis spores.
AuthorsPickering AK, Osorio M, Lee GM, Grippe VK, Bray M, Merkel TJ,
JournalInfect Immun
PubMed ID15501768
Bacillus anthracis, the etiological agent of anthrax, is a gram-positive, spore-forming bacterium. The inhalational form of anthrax is the most severe and is associated with rapid progression of the disease and the outcome is frequently fatal. Transfer from the respiratory epithelium to regional lymph nodes appears to be an essential ... More
CD4+ T-cell dysfunctions through the impaired lipid rafts ameliorate concanavalin A-induced hepatitis in sphingomyelin synthase 1-knockout mice.
AuthorsDong L, Watanabe K, Itoh M, Huan CR, Tong XP, Nakamura T, Miki M, Iwao H, Nakajima A, Sakai T, Kawanami T, Sawaki T, Masaki Y, Fukushima T, Fujita Y, Tanaka M, Yano M, Okazaki T, Umehara H,
JournalInt Immunol
PubMed ID22345277
Membrane microdomains consisting of sphingomyelin (SM) and cholesterol appear to be important for signal transduction in T-cell activation. The present study was designed to elucidate the role of membrane SM in vivo and in vitro using sphingomyelin synthase 1 (SMS1) knock out (SMS1(-/-)) mice and Concanavalin A (ConA)-induced hepatitis. After ... More
Toll-like receptor 4 plays a crucial role in the immune-adrenal response to systemic inflammatory response syndrome.
AuthorsZacharowski K, Zacharowski PA, Koch A, Baban A, Tran N, Berkels R, Papewalis C, Schulze-Osthoff K, Knuefermann P, Zähringer U, Schumann RR, Rettori V, McCann SM, Bornstein SR
JournalProc Natl Acad Sci U S A
PubMed ID16606831
Sepsis and septic shock are leading killers in the noncoronary intensive care unit, and they remain worldwide health concerns. The initial host defense against bacterial infections involves Toll-like receptors (TLRs), which detect and respond to microbial ligands. In addition, a coordinated response of the adrenal and immune systems is crucial ... More
Novel method of monitoring trace cytokines and activated STAT molecules in the paws of arthritic mice using multiplex bead technology.
AuthorsLu LD, Stump KL, Seavey MM
JournalBMC Immunol
PubMed ID21073728
The use of mouse models to study human disease provides useful data that can provide support for research projects or an existing drug discovery program. How well a model recapitulates the human condition and the ease and reproducibility of data collected will determine how much confidence a scientist can place ... More
Maternal exposure to secondhand cigarette smoke primes the lung for induction of phosphodiesterase-4D5 isozyme and exacerbated Th2 responses: rolipram attenuates the airway hyperreactivity and muscarinic receptor expression but not lung inflammation and atopy.
AuthorsSingh SP, Mishra NC, Rir-Sima-Ah J, Campen M, Kurup V, Razani-Boroujerdi S, Sopori ML
JournalJ Immunol
PubMed ID19596983
Airway hyperreactivity (AHR), lung inflammation, and atopy are clinical signs of allergic asthma. Gestational exposure to cigarette smoke (CS) markedly increases the risk for childhood allergic asthma. Muscarinic receptors regulate airway smooth muscle tone, and asthmatics exhibit increased AHR to muscarinic agonists. We have previously reported that in a murine ... More