Immunomodulatory effects of anti-CD4 antibody in host resistance against infections and tumors in human CD4 transgenic mice.
AuthorsHerzyk DJ, Gore ER, Polsky R, Nadwodny KL, Maier CC, Liu S, Hart TK, Harmsen AG, Bugelski PJ,
JournalInfect Immun
PubMed ID11160000
'Anti-CD4 antibodies, which cause CD4(+) T-cell depletion, have been shown to increase susceptibility to infections in mice. Thus, development of anti-CD4 antibodies for clinical use raises potential concerns about suppression of host defense mechanisms against pathogens and tumors. The anti-human CD4 antibody keliximab, which binds only human and chimpanzee CD4, ... More
Down-regulation of diabetogenic CD4+ T cells by a soluble dimeric peptide-MHC class II chimera.
AuthorsCasares S, Hurtado A, McEvoy RC, Sarukhan A, von Boehmer H, Brumeanu TD
JournalNat Immunol
PubMed ID11862219
'Type 1 diabetes is an organ-specific autoimmune disease that is mediated by autoreactive T cells. We show here that administration of a soluble dimeric peptide-major histocompatibility complex (pMHC) class II chimera (DEF) to prediabetic double-transgenic mice prevents the onset of disease or, in animals that are already diabetic, restores normoglycemia. ... More
Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure.
AuthorsLeonis MA, Toney-Earley K, Degen SJ, Waltz SE,
JournalHepatology
PubMed ID12395314
'The targeted deletion of the cytoplasmic domain of the Ron receptor tyrosine kinase (TK) in mice leads to exaggerated responses to injury in several murine models of inflammation as well as increased lethality in response to endotoxin (lipopolysaccharide [LPS]). Using a well-characterized model of LPS-induced acute liver failure (ALF) in ... More
Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice.
AuthorsKanters E, Pasparakis M, Gijbels MJ, Vergouwe MN, Partouns-Hendriks I, Fijneman RJ, Clausen BE, Förster I, Kockx MM, Rajewsky K, Kraal G, Hofker MH, de Winther MP,
JournalJ Clin Invest
PubMed ID14561702
'Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor NF-kappaB is a key regulator of inflammation, immune responses, cell survival, and cell proliferation. To investigate the role of NF-kappaB activation in macrophages during atherogenesis, we used LDL receptor-deficient mice with a macrophage-restricted deletion of IkappaB kinase ... More
An exaggerated inflammatory response after CLP correlates with a negative outcome.
AuthorsTorres MB, De Maio A,
JournalJ Surg Res
PubMed ID15836855
'Sepsis is the leading cause of morbidity and mortality in the surgical intensive care unit. We postulate that the variable clinical profile of septic patients is the product of multiple factors, including initiating insult, environment, and genetic make-up. This hypothesis was tested by changing the severity of the insult and ... More
Regulatory functions of self-restricted MHC class II allopeptide-specific Th2 clones in vivo.
AuthorsWaaga AM, Gasser M, Kist-van Holthe JE, Najafian N, Müller A, Vella JP, Womer KL, Chandraker A, Khoury SJ, Sayegh MH,
JournalJ Clin Invest
PubMed ID11285310
'We studied T-cell clones generated from grafts of rejecting and tolerant animals and investigated the regulatory function of Th2 clones in vitro and in vivo. To prevent allograft rejection, we treated LEW strain recipient rats of WF strain kidney grafts with CTLA4Ig to block CD28-B7 costimulation. We then isolated epitope-specific ... More
A model that reproduces syndromes associated with human multiple myeloma in nonirradiated SCID mice.
AuthorsBarton BE, Cullison J, Jackson J, Murphy T,
JournalProc Soc Exp Biol Med
PubMed ID10654623
'A human myeloma line was used to create a model of human multiple myeloma in vivo that would reproduce the pathophysiology of the disease, including the cachexia associated with cancer. Unirradiated severe combined immunodeficient (SCID) mice were used as surrogate hosts for in vivo experiments that allowed the effects of ... More
Pertussis toxin alters the innate and the adaptive immune responses in a pertussis-dependent model of autoimmunity.
AuthorsAgarwal RK, Sun SH, Su SB, Chan CC, Caspi RR,
JournalJ Neuroimmunol
PubMed ID12161029
'Pertussis toxin (PTX) is used to promote development of autoimmune diseases. The mechanism(s) are still incompletely understood. We dissected the innate and adaptive immune responses in a PTX-dependent model of autoimmune retinal disease, experimental autoimmune uveoretinitis (EAU), a Th1-driven disease of the neural retina elicited in F344 rats with a ... More
SHP-1-Pyk2-Src Protein Complex and p38 MAPK Pathways Independently Regulate IL-10 Production in Lipopolysaccharide-Stimulated Macrophages.
AuthorsOkenwa C, Kumar A, Rego D, Konarski Y, Nilchi L, Wright K, Kozlowski M,
Journal
PubMed ID23904162
'The role of tyrosine phosphatase Src homology region 2 domain-containing phosphatase (SHP)-1 in LPS-activated cytokine production and inflammation was investigated by determining TNF-a and IL-10 production in splenic macrophages employing SHP-1-null (me/me) mouse model. LPS-stimulated me/me splenic macrophages secreted significantly less IL-10 with concomitantly elevated levels of TNF-a compared with ... More
Protein kinase C ? deficiency increases resistance of C57BL/6J mice to Plasmodium berghei infection-induced cerebral malaria.
AuthorsOhayon A, Golenser J, Sinay R, Tamir A, Altman A, Pollack Y, Isakov N
JournalInfect Immun
PubMed ID20660606
'Protein kinase C ? (PKC?) functions as a core component of the immunological synapse and serves as a key protein in the integrated T-cell antigen receptor (TCR)/CD28-induced signaling cascade leading to T-cell activation. However, the involvement of PKC? in host-mediated immune responses to pathogens has not been thoroughly investigated. We ... More
Interleukin-1 receptor signaling protects mice from lethal intestinal damage caused by the attaching and effacing pathogen Citrobacter rodentium.
'Enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter rodentium are classified as attaching and effacing pathogens based on their ability to adhere to the intestinal epithelium via actin-filled membranous protrusions (pedestals). Infection of mice with C. rodentium causes a breach of the intestinal epithelial barrier, leading to colitis via a ... More
Prevention and reversal of experimental autoimmune myasthenia gravis by a monoclonal antibody against acetylcholine receptor-specific T cells.
AuthorsXu L, Villain M, Galin FS, Araga S, Blalock JE,
JournalCell Immunol
PubMed ID11333143
We have recently described an algorithm to design, among others, peptides with complementarity contour to autoimmune epitopes. Immunization with one such peptide resulted in a monoclonal antibody (mAb), termed CTCR8, that specifically recognized Vbeta15 containing TCR on acetylcholine receptor (AChR) alpha-chain residue 100-116-specific T cells. CTCR8 was found to label ... More
Viral IL-10-mediated immune regulation in pancreatic islet transplantation.
AuthorsCarter JD, Ellett JD, Chen M, Smith KM, Fialkow LB, McDuffie MJ, Tung KS, Nadler JL, Yang Z,
JournalMol Ther
PubMed ID16043104
Protection of transplanted pancreatic islet grafts in recipients with autoimmune diabetes depends on the suppression of autoimmune recurrence and allogeneic rejection. The aim of this study was to investigate the efficiency of viral IL-10 gene delivery in the prevention of autoimmune recurrence following islet transplantation. We evaluated the effectiveness of ... More
Influenza infection promotes macrophage traffic into arteries of mice that is prevented by D-4F, an apolipoprotein A-I mimetic peptide.
We reported that HDL loses its antiinflammatory properties during acute influenza A infection in mice, and we hypothesized that these changes might be associated with increased trafficking of macrophages into the artery wall. The present study tested this hypothesis. D-4F, an apolipoprotein A-I mimetic peptide, or vehicle in which it ... More
Construction and immunogenicity of recombinant Mycobacterium bovis BCG expressing GP5 and M protein of porcine reproductive respiratory syndrome virus.
AuthorsBastos RG, Dellagostin OA, Barletta RG, Doster AR, Nelson E, Osorio FA,
JournalVaccine
PubMed ID12443659
Mycobacterium bovis BCG was used to express a truncated form of GP5 (lacking the first 30 NH(2)-terminal residues) and M protein of porcine reproductive and respiratory syndrome virus (PRRSV). The PRRSV proteins were expressed in BCG under control of the mycobacterial hsp60 gene promoter either in the mycobacterial cytoplasm (BCGGP5cyt ... More
Suppression of gamma interferon transcription and production by nematode excretory-secretory antigen during polyclonal stimulation of rat lymph node T cells.
AuthorsUchikawa R, Matsuda S, Arizono N,
JournalInfect Immun
PubMed ID11035730
Although certain helminth infections preferentially induce type 2 T-cell responses, the immunological mechanisms responsible for type 2 T-cell polarization remain unclear. In the present study, we investigated the effects of excretory-secretory (ES) antigen from the nematode Nippostrongylus brasiliensis on cytokine production by mesenteric lymph node (MLN) cells isolated from naive ... More
Protective DNA vaccination against organ-specific autoimmunity is highly specific and discriminates between single amino acid substitutions in the peptide autoantigen.
AuthorsWeissert R, Lobell A, de Graaf KL, Eltayeb SY, Andersson R, Olsson T, Wigzell H,
JournalProc Natl Acad Sci U S A
PubMed ID10677519
DNA vaccines that encode encephalitogenic sequences in tandem can protect from subsequent experimental autoimmune encephalomyelitis induced with the corresponding peptide. The mechanism for this protection and, in particular, if it is specific for the amino acid sequence encoding the vaccine are not known. We show here that a single amino ... More
A key role for prostaglandin I2 in limiting lung mucosal Th2, but not Th1, responses to inhaled allergen.
AuthorsJaffar Z, Wan KS, Roberts K,
JournalJ Immunol
PubMed ID12421986
The cellular events that serve to regulate lung mucosal Th2 responses and limit allergic inflammatory reactions are unclear. Using the DO11.10 TCR transgenic mouse, we developed a model of T cell-mediated pulmonary inflammation and demonstrated that high levels of PGI(2) are produced in the airways following OVA inhalation. Selective inhibition ... More
Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice.
AuthorsVaid M, Singh T, Prasad R, Elmets CA, Xu H, Katiyar SK,
JournalCancer Prev Res (Phila)
PubMed ID23321928
Ultraviolet (UV) radiation-induced immunosuppression has been implicated in skin carcinogenesis. Grape seed proanthocyanidins (GSPs) have anti-skin carcinogenic effects in mice and GSPs-fed mice exhibit a reduction in UV-induced suppression of allergic contact hypersensitivity (CHS), a prototypic T-cell-mediated response. Here, we report that dietary GSPs did not inhibit UVB-induced suppression of ... More
Impact of alcohol intoxication on hemodynamic, metabolic, and cytokine responses to hemorrhagic shock.
Alcohol intoxication is associated with a high incidence of traumatic injury, particularly in the young healthy population. The impact of alcohol intoxication on the immediate pathophysiologic response to injury has not been closely examined. We hypothesized that acute alcohol intoxication would aggravate the immediate outcome from hemorrhagic shock by impairing ... More
Vitamin D3 modulates the expression of bile acid regulatory genes and represses inflammation in bile duct-ligated mice.
AuthorsOgura M, Nishida S, Ishizawa M, Sakurai K, Shimizu M, Matsuo S, Amano S, Uno S, Makishima M,
JournalJ Pharmacol Exp Ther
PubMed ID18988769
Vitamin D receptor (VDR), a nuclear receptor that regulates calcium homeostasis, has been found to function as a receptor for secondary bile acids. Because the in vivo role of VDR in bile acid metabolism remains unknown, we investigated the effect of VDR activation in a mouse model of cholestasis. We ... More
Primary infection of mice with high titer inoculum respiratory syncytial virus: characterization and response to antiviral therapy.
AuthorsBolger G, Lapeyre N, Dansereau N, Lagacé L, Berry G, Klosowski K, Mewhort T, Liuzzi M,
JournalCan J Physiol Pharmacol
PubMed ID15791294
Intranasal infection of BALB/c mice with respiratory syncytial virus (RSV)-A2 (0.5 x 10(8) - 2.0 x 10(8) plaque-forming units, PFU) produced disease characterized by weight loss (2-3 g) and mortality (60%-100%) with the mean day of death ranging from 6-7 d after infection. The extent of RSV disease was inoculum ... More
Suppression of autoimmune diabetes by viral IL-10 gene transfer.
AuthorsYang Z, Chen M, Wu R, Fialkow LB, Bromberg JS, McDuffie M, Naji A, Nadler JL
JournalJ Immunol
PubMed ID12055268
Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the up-regulation of proinflammatory activity that leads to destruction of insulin-producing pancreatic beta cells in type 1 diabetes. Th2-type cytokines, such as IL-10, have immune regulatory function. Administration of IL-10, or IL-10 gene transfer, prevents autoimmune ... More
Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice.
AuthorsYao M, Kargman S, Lam EC, Kelly CR, Zheng Y, Luk P, Kwong E, Evans JF, Wolfe MM
JournalCancer Res
PubMed ID12566300
A large number of epidemiological studies have shown that regular use of aspirinor other nonsteroidal anti-inflammatory drugs (NSAIDs) results in a 40-50% reduced risk of colorectal cancer (CRC). Furthermore, NSAIDs cause the regression of preexisting adenomas in patients with familial adenomatous polyposis and significantly inhibit tumor growth in animal models ... More