AuthorsTuaillon N, Shen DF, Berger RB, Lu B, Rollins BJ, Chan CC,
JournalInvest Ophthalmol Vis Sci
PubMed ID11980865
Monocyte chemoattractant protein (MCP)-1 (CCL-2) is a chemokine with chemoattractant properties for monocytes, memory T cells, natural killer cells, mast cells, and basophils. To delineate the role played by MCP-1 in acute anterior uveitis, a common ocular inflammation, MCP-1(-/-) mice and wild-type matched control mice were analyzed for the development ... 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
Interleukin-6 deficiency increases inflammatory bone destruction.
AuthorsBalto K, Sasaki H, Stashenko P,
JournalInfect Immun
PubMed ID11159963
'Periapical bone destruction occurs as a consequence of pulpal infection. In previous studies, we showed that interleukin-1 (IL-1) is the primary stimulator of bone destruction in this model. IL-6 is a pleiotropic cytokine that is induced in these infections and has both pro- and anti-inflammatory activities. In the present study, ... More
Increased immune response in mice consuming rice bran oil.
'Polyunsaturated fatty acids play a key role in a number of biological functions. Rice bran oil (RBO) is rich in linoleic acid, an essential n-6 fatty acid. n-6 fatty acids are said to have proinflammatory effects as a result of an increase in n-6 fatty acid-derived eicosanoids. RBO is also ... More
Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation.
AuthorsZheng D, Giljohann DA, Chen DL, Massich MD, Wang XQ, Iordanov H, Mirkin CA, Paller AS,
JournalProc Natl Acad Sci U S A
PubMed ID22773805
'Topical application of nucleic acids offers many potential therapeutic advantages for suppressing genes in the skin, and potentially for systemic gene delivery. However, the epidermal barrier typically precludes entry of gene-suppressing therapy unless the barrier is disrupted. We now show that spherical nucleic acid nanoparticle conjugates (SNA-NCs), gold cores surrounded ... More
Interleukin-10-independent anti-inflammatory actions of glucagon-like peptide 2.
AuthorsIvory CP, Wallace LE, McCafferty DM, Sigalet DL,
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID18845573
'Glucagon-like peptide 2 (GLP-2) is an important intestinal growth factor with anti-inflammatory activity. We hypothesized that GLP-2 decreases mucosal inflammation and the associated increased epithelial proliferation by downregulation of Th1 cytokines attributable to reprogramming of lamina propria immune regulatory cells via an interleukin-10 (IL-10)-independent pathway. The effects of GLP-2 treatment ... 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
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
Macrophage-derived cell lines do not express proinflammatory cytokines after exposure to Bacillus anthracis lethal toxin.
We present evidence that Bacillus anthracis lethal toxin (LT) suppresses rather than induces proinflammatory cytokine production in macrophages. Suppression is observed with extremely low levels of LT and involves inhibition of transcription of cytokine messenger RNA. Thus, LT may contribute to anthrax pathogenesis by suppressing the inflammatory response. ... More
Activation of the endocannabinoid system as therapeutic approach in a murine model of multiple sclerosis.
AuthorsOrtega-Gutiérrez S, Molina-Holgado E, Arévalo-Martín A, Correa F, Viso A, López-Rodríguez ML, Di Marzo V, Guaza C,
JournalFASEB J
PubMed ID15941768
Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a well-characterized murine model of human multiple sclerosis (MS) that closely resembles the chronic and progressive clinical form of the disease. Recent studies have described the involvement of the cannabinoid system in the progression of the disease and the benefits associated with ... More
Macrophage colony-stimulating factor and its receptor signaling augment glycated albumin-induced retinal microglial inflammation in vitro.
AuthorsLiu W, Xu GZ, Jiang CH, Tian J
JournalBMC Cell Biol
PubMed ID21266043
Microglial activation and the proinflammatory response are controlled by a complex regulatory network. Among the various candidates, macrophage colony-stimulating factor (M-CSF) is considered an important cytokine. The up-regulation of M-CSF and its receptor CSF-1R has been reported in brain disease, as well as in diabetic complications; however, the mechanism is ... More
Effects of interferon-beta on the cytokine production of astrocytes.
AuthorsOkada K, Kuroda E, Yoshida Y, Yamashita U, Suzumura A, Tsuji S,
JournalJ Neuroimmunol
PubMed ID15652402
The effects of interferon (IFN)-beta used for treatment of multiple sclerosis (MS) on the central nervous system (CNS) have not yet been elucidated. The effect of IFN-beta and IFN-gamma on astrocytes as the major component of the CNS was investigated using murine primary astrocytes and human astrocytoma U251 cell line. ... More
Aryl hydrocarbon receptor mediates both proinflammatory and anti-inflammatory effects in lipopolysaccharide-activated microglia.
AuthorsLee YH, Lin CH, Hsu PC, Sun YY, Huang YJ, Zhuo JH, Wang CY, Gan YL, Hung CC, Kuan CY, Shie FS,
Journal
PubMed ID25690886
The aryl hydrocarbon receptor (AhR) regulates peripheral immunity; but its role in microglia-mediated neuroinflammation in the brain remains unknown. Here, we demonstrate that AhR mediates both anti-inflammatory and proinflammatory effects in lipopolysaccharide (LPS)-activated microglia. Activation of AhR by its ligands, formylindolo[3,2-b]carbazole (FICZ) or 3-methylcholanthrene (3MC), attenuated LPS-induced microglial immune responses. ... More
Hyperoxia-induced hypertrophy and ion channel remodeling in left ventricle.
AuthorsPanguluri SK, Tur J, Fukumoto J, Deng W, Sneed KB, Kolliputi N, Bennett ES, Tipparaju SM,
JournalAm J Physiol Heart Circ Physiol
PubMed ID23585127
Ventricular arrhythmias account for high mortality in cardiopulmonary patients in intensive care units. Cardiovascular alterations and molecular-level changes in response to the commonly used oxygen treatment remains unknown. In the present study we investigated cardiac hypertrophy and cardiac complications in mice subjected to hyperoxia. Results demonstrate that there is a ... More
PKC epsilon is involved in JNK activation that mediates LPS-induced TNF-alpha, which induces apoptosis in macrophages.
AuthorsComalada M, Xaus J, Valledor AF, López-López C, Pennington DJ, Celada A,
JournalAm J Physiol Cell Physiol
PubMed ID12867362
Lipopolysaccharide (LPS) is a powerful stimulator of macrophages and induces apoptosis in these cells. Using primary cultures of bone marrow-derived macrophages, we found that the autocrine production of tumor necrosis factor-alpha (TNF-alpha) has a major function in LPS-induced apoptosis. LPS activates PKC and regulates the different mitogen-activated protein kinases (MAPK). ... More
Heat-shock pre-treatment reduces liver injury and aids liver recovery after partial hepatectomy in mice.
AuthorsOka Y, Akagi Y, Kinugasa T, Ishibashi N, Iwakuma N, Shiratsuchi I, Shirouzu K,
Journal
PubMed ID23780975
Heat-shock proteins (HSPs) are members of a chaperone protein family reported to modify stress responses. The aim of this study was to clarify the hypothesis of whether pre-treatment with heat shock reduces liver damage and influences liver regeneration after partial hepatectomy. Mice (N=6) were divided into two groups: the control ... More
Retinol-binding protein 4 inhibits insulin signaling in adipocytes by inducing proinflammatory cytokines in macrophages through a c-Jun N-terminal kinase- and toll-like receptor 4-dependent and retinol-independent mechanism.
AuthorsNorseen J, Hosooka T, Hammarstedt A, Yore MM, Kant S, Aryal P, Kiernan UA, Phillips DA, Maruyama H, Kraus BJ, Usheva A, Davis RJ, Smith U, Kahn BB,
JournalMol Cell Biol
PubMed ID22431523
Retinol-binding protein 4 (RBP4), the sole retinol transporter in blood, is secreted from adipocytes and liver. Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. Here we show that RBP4 induces expression ... 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
The ScpC protease of Streptococcus pyogenes affects the outcome of sepsis in a murine model.
AuthorsSjölinder H, Lövkvist L, Plant L, Eriksson J, Aro H, Jones A, Jonsson AB,
JournalInfect Immun
PubMed ID18573900
The ScpC protease of Streptococcus pyogenes degrades interleukin-8 (IL-8), a chemokine that mediates neutrophil transmigration and activation. The ability to degrade IL-8 differs dramatically among clinical isolates of S. pyogenes. Bacteria expressing ScpC overcome immune clearance by preventing the recruitment of neutrophils in soft tissue infection of mice. To study ... More
Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter.
AuthorsWilliams MA, Rangasamy T, Bauer SM, Killedar S, Karp M, Kensler TW, Yamamoto M, Breysse P, Biswal S, Georas SN,
JournalJ Immunol
PubMed ID18802057
Oxidative stress is important in dendritic cell (DC) activation. Environmental particulate matter (PM) directs pro-oxidant activities that may alter DC function. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates expression of antioxidant and detoxification genes. Oxidative stress and defective antioxidant responses may contribute to ... More
Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA.
AuthorsKarikó K, Muramatsu H, Ludwig J, Weissman D,
JournalNucleic Acids Res
PubMed ID21890902
In vitro-transcribed mRNA has great therapeutic potential to transiently express the encoded protein without the adverse effects of viral and DNA-based constructs. Mammalian cells, however, contain RNA sensors of the innate immune system that must be considered in the generation of therapeutic RNA. Incorporation of modified nucleosides both reduces innate ... More
Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation.
AuthorsChung YC, Bok E, Huh SH, Park JY, Yoon SH, Kim SR, Kim YS, Maeng S, Hyun Park S, Jin BK,
JournalJ Immunol
PubMed ID22079984
This study examined whether the cannabinoid receptor type 1 (CB(1)) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or ... More
Positive and negative regulation of high affinity IgE receptor signaling by Src homology region 2 domain-containing phosphatase 1.
AuthorsNakata K, Yoshimaru T, Suzuki Y, Inoue T, Ra C, Yakura H, Mizuno K,
JournalJ Immunol
PubMed ID18832698
Src homology region 2 domain-containing phosphatase 1 (SHP-1), a cytoplasmic protein tyrosine phosphatase, plays an important role for the regulation of signaling from various hematopoietic cell receptors. Although SHP-1 is shown to be a negative signal modulator in mast cells, its precise molecular mechanisms are not well defined. To elucidate ... More
Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance.
High mobility group box protein 1 (HMGB1) modulates the innate immune response when present in the extracellular compartment. Receptors for HMGB1 include TLR4, TLR2, and the receptor for advanced glycation end products (RAGE). We tested the hypothesis that extracellular HMGB1 can induce LPS tolerance. HMGB1 dose-response experiments were performed on ... More
RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis.
AuthorsTurovskaya O, Foell D, Sinha P, Vogl T, Newlin R, Nayak J, Nguyen M, Olsson A, Nawroth PP, Bierhaus A, Varki N, Kronenberg M, Freeze HH, Srikrishna G,
JournalCarcinogenesis
PubMed ID18689872
Patients with inflammatory bowel diseases are at increased risk for colorectal cancer, but the molecular mechanisms linking inflammation and cancer are not well defined. We earlier showed that carboxylated N-glycans expressed on receptor for advanced glycation end products (RAGE) and other glycoproteins mediate colitis through activation of nuclear factor kappa ... More
Adverse effect of a presenilin-1 mutation in microglia results in enhanced nitric oxide and inflammatory cytokine responses to immune challenge in the brain.
AuthorsLee J, Chan SL, Mattson MP,
JournalNeuromolecular Med
PubMed ID12230303
Inflammatory processes involving glial cell activation are associated with amyloid plaques and neurofibrillary tangles, the cardinal neuropathological lesions in the brains of Alzheimer's disease (AD) patients, However, it is unclear whether these inflammatory processes occur as a response to neuronal degeneration or might represent more seminal events in the disease ... More
Modulation of interleukin-12 synthesis by DNA lacking the CpG motif and present in a mycobacterial cell wall complex.
A mycobacterial cell wall complex prepared from the non-pathogenic microorganism Mycobacterium phlei, where mycobacterial DNA is preserved and complexed to cell wall fragments, possesses anticancer and immunomodulatory activity. DNA from a number of prokaryotes has been found to modulate the immune system and to induce cytokine synthesis. We have therefore ... More
Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock.
AuthorsSekine H, Mimura J, Oshima M, Okawa H, Kanno J, Igarashi K, Gonzalez FJ, Ikuta T, Kawajiri K, Fujii-Kuriyama Y,
JournalMol Cell Biol
PubMed ID19822660
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is known to mediate a wide variety of pharmacological and toxicological effects caused by polycyclic aromatic hydrocarbons. Recent studies have revealed that AhR is involved in the normal development and homeostasis of many organs. Here, we demonstrate that AhR knockout (AhR KO) ... More
Toll-like receptor 4-deficient mice have reduced bone destruction following mixed anaerobic infection.
AuthorsHou L, Sasaki H, Stashenko P,
JournalInfect Immun
PubMed ID10899873
C3H/HeJ mice have an impaired ability to respond to lipopolysaccharide (LPS) due to a mutation in the gene that encodes Toll-like receptor 4 (TLR4). The effect of TLR4 deficiency on host responses to endodontic infections is unknown. In the present study, we compared periapical bone destruction, sepsis, and inflammatory cytokine ... 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
The FcRß- and ?-ITAMs play crucial but distinct roles in the full activation of mast cells induced by IgE? and Protein L.
AuthorsNunomura S, Kawakami Y, Kawakami T, Ra C
JournalJ Immunol
PubMed ID22430736
Previous studies suggested that Protein L (PpL), the bacterial Ig-binding protein, activates mast cells. PpL presumably performs the activation by interacting with membrane-bound IgE?, but the underlying mechanisms behind the process remain unclear. In the current study, we found that cell-surface FceRI expression is a critical factor participant in PpL-mediated ... More