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Potential Therapeutic Role (potential + therapeutic_role)

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Medical Sciences	100%

Selected Abstracts

Protective role of osteopontin in endodontic infection

IMMUNOLOGY, Issue 1 2010
Susan R. Rittling
Summary Endodontic infections are polymicrobial infections resulting in bone destruction and tooth loss. The host response to these infections is complex, including both innate and adaptive mechanisms. Osteopontin (OPN), a secreted, integrin-binding protein, functions in the regulation of immune responses and enhancement of leucocyte migration. We have assessed the role of OPN in the host response to endodontic infection using a well-characterized mouse model. Periapical bone loss associated with endodontic infection was significantly more severe in OPN-deficient mice compared with wild-type 3 weeks after infection, and was associated with increased areas of inflammation. Expression of cytokines associated with bone loss, interleukin-1, (IL-1,) and RANKL, was increased 3 days after infection. There was little effect of OPN deficiency on the adaptive immune response to these infections, as there was no effect of genotype on the ratio of bacteria-specific immunoglobulin G1 and G2a in the serum of infected mice. Furthermore, there was no difference in the expression of cytokines associated with T helper type 1/type2 balance: IL-12, IL-10 and interferon-,. In infected tissues, neutrophil infiltration into the lesion area was slightly increased in OPN-deficient animals 3 days after infection: this was confirmed by a significant increase in expression of neutrophil elastase in OPN-deficient samples at this time-point. We conclude that OPN has a protective effect on polymicrobial infection, at least partially because of alterations in phagocyte recruitment and/or persistence at the sites of infection, and that this molecule has a potential therapeutic role in polymicrobial infections. [source]

Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice

INFLAMMATORY BOWEL DISEASES, Issue 2 2002
Michael Schultz
Abstract Interleukin (IL)-10-deficient (IL-10,/,) mice develop colitis under specific pathogen-free (SPF) conditions and remain disease free if kept sterile (germ free [GF]). We used four different protocols that varied the time-points of oral administration of Lactobacillus plantarum 299v (L. plantarum) relative to colonization with SPF bacteria to determine whether L. plantarum could prevent and treat colitis induced by SPF bacteria in IL-10,/, mice and evaluated the effect of this probiotic organism on mucosal immune activation. Assessment of colitis included blinded histologic scores, measurements of secreted colonic immunoglobulin isotypes, IL-12 (p40 subunit), and interferon (IFN)-, production by anti-CD3-stimulated mesenteric lymph node cells. Treating SPF IL-10,/, mice with L. plantarum attenuated previously established colonic inflammation as manifested by decreased mucosal IL-12, IFN-,, and immunoglobulin G2a levels. Colonizing GF animals with L. plantarum and SPF flora simultaneously had no protective effects. Gnotobiotic IL-10,/, mice monoassociated with L. plantarum exhibited mild immune system activation but no colitis. Pretreatment of GF mice by colonization with L. plantarum, then exposure to SPF flora and continued probiotic therapy significantly decreased histologic colitis scores. These results demonstrate that L. plantarum can attenuate immune-mediated colitis and suggest a potential therapeutic role for this agent in clinical inflammatory bowel diseases. [source]

In Utero Ethanol Exposure Impairs Defenses Against Experimental Group B Streptococcus in the Term Guinea Pig Lung

ALCOHOLISM, Issue 2 2009
Theresa W. Gauthier
Background:, The effects of fetal alcohol exposure on the risks of neonatal lung injury and infection remain under investigation. The resident alveolar macrophage (AM) is the first line of immune defense against pulmonary infections. In utero ethanol (ETOH) exposure deranges the function of both premature and term guinea pig AM. We hypothesized that fetal ETOH exposure would increase the risk of pulmonary infection in vivo. Methods:, We developed a novel in vivo model of group B Streptococcus (GBS) pneumonia using our established guinea pig model of fetal ETOH exposure. Timed-pregnant guinea pigs were pair fed ±ETOH and some were supplemented with the glutathione (GSH) precursor S -adenosyl-methionine (SAM-e). Term pups were given GBS intratracheally while some were pretreated with inhaled GSH prior to the experimental GBS. Neonatal lung and whole blood were evaluated for GBS while isolated AM were evaluated using fluorescent microscopy for GBS phagocytosis. Results:, Ethanol-exposed pups demonstrated increased lung infection and sepsis while AM phagocytosis of GBS was deficient compared with control. When SAM-e was added to the maternal diet containing ETOH, neonatal lung and systemic infection from GBS was attenuated and AM phagocytosis was improved. Inhaled GSH therapy prior to GBS similarly protected the ETOH-exposed pup from lung and systemic infection. Conclusions:, In utero ETOH exposure impaired the neonatal lung's defense against experimental GBS, while maintaining GSH availability protected the ETOH-exposed lung. This study suggested that fetal alcohol exposure deranges the neonatal lung's defense against bacterial infection, and support further investigations into the potential therapeutic role for exogenous GSH to augment neonatal AM function. [source]

Modulation of adenovirus infection in vitro by antisense oligodeoxynucleotides

RESPIROLOGY, Issue 3 2003
Bruce F. WHITEHEAD
Objective: Antisense oligodeoxynucleotides (ODNs) may represent a novel, airway directed approach to the treatment of adenovirus infection of the lung, for which no specific therapy exists. This study assessed the efficacy of antisense ODNs in modulating adenovirus infection in vitro. Methodology: A biological assay, which quantified viral plaque formation by wild type adenovirus 5 in a lung epithelial cell line (A549), was used to evaluate the inhibitory effect of a number of antisense ODNs targeted to the early (E) 1 A and protein IX genes of adenovirus 5. Antisense ODNs (20,21mers, phosphorothioate end-protected) were designed to straddle the initiation of translation (AUG) codon of the mRNA of the targeted gene. Results: There was a consistent and significant (P < 0.005) reduction in viral plaque formation in those cells treated with an E1A antisense ODN, compared with the nonsense control ODN. Neither the addition of a cationic lipid (Lipofectamine), nor increasing the concentration of ODN from 1 µmol to 15 µmol enhanced the original inhibitory effect observed with the E1A antisense ODN. Conclusions: An antisense ODN targeted to the E1A gene can specifically inhibit adenovirus 5 infection in vitro, suggesting a potential therapeutic role for antisense ODNs in adenovirus infection of the lung. [source]