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
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
IL-12-independent Th1-type immune responses to respiratory viral infection: requirement of IL-18 for IFN-gamma release in the lung but not for the differentiation of viral-reactive Th1-type lymphocytes.
AuthorsXing Z, Zganiacz A, Wang J, Divangahi M, Nawaz F,
JournalJ Immunol
PubMed ID10679096
'We demonstrated that IL-12 was induced during primary or secondary pulmonary adenoviral infection in wild-type (wt) mice. However, cellular responses were not compromised in the lungs of IL-12-/- mice. The level of IFN-gamma in the lung was similar in wt and IL-12-/- mice during pulmonary viral infection. Upon Ag stimulation ... More
Enhanced protection against fatal mycobacterial infection in SCID beige mice by reshaping innate immunity with IFN-gamma transgene.
AuthorsXing Z, Zganiacz A, Wang J, Sharma SK,
JournalJ Immunol
PubMed ID11418673
Humans with immune-compromised conditions such as SCID are unable to control infection caused by normally nonpathogenic intracellular pathogens such as Mycobacterium bovis bacillus Calmette-Guérin. We found that SCID beige mice lacking both lymphocytes and NK cells had functionally normal lung macrophages and yet a selectively impaired response of type 1 ... More
Natural killer cells participate in bacterial clearance during septic peritonitis through interactions with macrophages.
AuthorsGodshall CJ, Scott MJ, Burch PT, Peyton JC, Cheadle WG,
JournalShock
PubMed ID12578123
Natural killer (NK) cells have a well-established role in host defense against viral infections and malignancies. However, their function in bacterial infection and sepsis is poorly defined. We hypothesized that NK cells, as a major producer of interferon-gamma during sepsis, would be important in host defense against bacterial infections. Cecal ... More
AuthorsBalicki D, Reisfeld RA, Pertl U, Beutler E, Lode HN,
JournalProc Natl Acad Sci U S A
PubMed ID11016973
A major goal of cancer immunotherapy is the induction of a cell-mediated antitumor response in poorly immunogenic malignancies. We tested the hypothesis that this can be achieved by cytokine gene therapy with a novel histone H2A-based transient transfection procedure. This was tested by using cytokine genes encoding for IL-2 and ... 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
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
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
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
Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function.
AuthorsWhyte CS, Bishop ET, Rückerl D, Gaspar-Pereira S, Barker RN, Allen JE, Rees AJ, Wilson HM
JournalJ Leukoc Biol
PubMed ID21628332
Macrophages become activated by their environment and develop polarized functions: classically activated (M1) macrophages eliminate pathogens but can cause tissue injury, whereas alternatively activated (M2) macrophages promote healing and repair. Mechanisms directing polarized activation, especially in vivo, are not understood completely, and here, we examined the role of SOCS proteins. ... 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