IL-10 delivery by AAV5 vector attenuates inflammation in mice with pseudomonas pneumonia

Buff, Scotty M.; Yu, Hong; McCall, J. N.; Caldwell, Sydney; Ferkol, Thomas; Flotte, Terence R.; Virella‐Lowell, Isabel

doi:10.1038/gt.2010.28

Cited by 30 publications

(26 citation statements)

References 63 publications

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“…Anti-inflammatory effects of MSC transplantation might include immune modulation 36 and delivery of various growth factors and cytokines, such as vascular endothelial growth factor, hepatocyte growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and IL-10. 13,[37][38][39] By secreting these trophic factors, MSCs might promote a shift from a proinflammatory environment toward an anti-inflammatory or tolerant environment. 40 Further studies will be necessary to identify the trophic factors secreted from transplanted stem cells that might mediate this anti-inflammatory effect.…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal Stem Cells Prevent Hydrocephalus After Severe Intraventricular Hemorrhage

Ahn

Chang²,

Sung³

et al. 2013

Stroke

152

219

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I ntraventricular hemorrhage (IVH) is a serious complication of preterm birth, and the number of infants at high risk for developing IVH is increasing as a result of the rise in the absolute number and improved survival of very premature infants with recent advances in neonatal intensive care medicine. 1,2 Over half of infants with severe IVH (grade ≥3) die or develop posthemorrhagic hydrocephalus (PHH), which requires shunt surgery in up to 70% of cases.3 IVH is associated with brain damage, especially to the periventricular white matter, which is exacerbated by PHH, and finally results in increased mortality and long-term neurological morbidity, such as seizure, cerebral palsy, and developmental retardation in survivors. [4][5][6] Until now, however, there has not been any effective treatment to prevent PHH or ameliorate brain damage after severe IVH in preterm infants, so it remains a major problem of neonatal intensive care.Although the precise mechanism has not been completely delineated, the pathogenesis of communicating progressive posthemorrhagic ventricular dilatation has been explained by inflammation within subarachnoid spaces attributable to blood contact and deposition of blood products. 7,8 This obliterative arachnoiditis leads to dysfunction of arachnoid granulations, which reduces cerebrospinal fluid (CSF) resorption and increases intracranial pressure, resulting in venous infarction with decreased cerebral perfusion. 8 Moreover, inflammatory cytokines originating from blood products in the cerebral ventricles may injure the periventricular white matter. 9,10 Therefore, new therapeutic modalities with anti-inflammatory capabilities to treat PHH and brain damage after severe IVH would be of great value.Recent preclinical research reported that an anti-inflammatory agent, a cycloxygenase-2 inhibitor, noticeably reduced reactive gliosis and improved neurological impairment after IVH in a newborn rabbit model. This finding indicates that modulating inflammation could be a key factor in IVH therapy for preterm Background and Purpose-Severe intraventricular hemorrhage (IVH) in premature infants and the ensuing posthemorrhagic hydrocephalus cause significant mortality and neurological disabilities, and there are currently no effective therapies. This study determined whether intraventricular transplantation of human umbilical cord blood-derived mesenchymal stem cells prevents posthemorrhagic hydrocephalus development and attenuates brain damage after severe IVH in newborn rats. Methods-To induce severe IVH, 100 μL of blood was injected into each lateral ventricle of postnatal day 4 (P4) SpragueDawley rats. Human umbilical cord blood-derived mesenchymal stem cells or fibroblasts (1×10 5 ) were transplanted intraventricularly under stereotaxic guidance at P6. Serial brain MRI and behavioral function tests, such as the negative geotaxis test and rotarod test, were performed. At P32, brain tissue and cerebrospinal fluid were obtained for histological and biochemical analyses. Results-Intraventricular tran...

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Section: Discussionmentioning

confidence: 99%

“…Enzyme-linked immunosorbent assay (ELISA) 37 Frozen samples of the periventricular zone of brain tissue were homogenized and centrifuged 38 at 8,000 g for 20 minutes at 4°C. The protein content in the supernatant was measured using 39 the Bradford method with bovine serum albumin (Sigma-Aldrich) as a standard. 40 41 Tracking of donor cells…”

Section: Disclosuresmentioning

confidence: 99%

Mesenchymal Stem Cells Prevent Hydrocephalus After Severe Intraventricular Hemorrhage

Ahn

Chang²,

Sung³

et al. 2013

Stroke

152

219

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“…Assay development and optimization were conducted in the following order: (i) optimization of capture antibody concentrations, (ii) optimization of detection antibody concentrations, (iii) determination of standard curve ranges, (iv) evaluation of cross-reactivity among analytes, (v) comparison of MFI between single and multiplex standard curves, (vi) optimization of streptavidin-PE concentration, and (vii) optimization of the number of microspheres per well. Capture antibody concentrations tested were 1, 2.5, 5, 7.5, 10, and 15 g per 10 6 microspheres. Detection antibody concentrations tested were 1ϫ, 2ϫ, and 3ϫ the recommended concentration for ELISA protocols.…”

Section: Methodsmentioning

confidence: 99%

“…There are commercially available cytokine-multiplex kits for humans, nonhuman primates, mice, rats, and dogs; however, no kits are currently available for domestic cats. The availability of human and mouse reagents has allowed the analysis of cytokine levels in a variety of disease states, including sickle cell disease (1), sepsis (5), and viral infection in humans (8) and bacterial pneumonia in mice (6). The capacity to accurately and reproducibly evaluate cytokine profiles in domestic cats, in both naturally occurring and experimentally induced disease states, would potentially provide valuable information regarding disease pathogenesis, progression, and prognosis.…”

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confidence: 99%

Development and Validation of a Multiplex Microsphere-Based Assay for Detection of Domestic Cat ( Felis catus ) Cytokines

Wood

O’Halloran

VandeWoude

2011

Clin Vaccine Immunol

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Cytokines are essential signaling molecules that mediate the innate immune response, and therefore their presence can be of diagnostic, prognostic, and pathogenic significance. Microsphere-based immunoassays allow rapid and accurate evaluation of cytokine levels in several species, including humans, dogs, and mice; however, technology to evaluate domestic cat (Felis catus) cytokines has been limited to single-analyte enzymelinked immunosorbent assays (ELISAs). Microsphere-based immunoassays provide an attractive alternative technology for detecting and quantifying multiple analytes in a single assay using as little as 50 l of sample. We describe the development and validation of a microsphere-based assay for three commonly analyzed domestic cat cytokines (gamma interferon, interleukin-10, and interleukin-12/interleukin-23 p40) using reagents from commercially available ELISAs. The assay was optimized for capture and detection antibody concentrations, streptavidin-phycoerythrin concentration, and number of microspheres. The validated lower and upper quantitation limits were 31 and 1,000 pg/ml for gamma interferon, 63 and 2,000 pg/ml for interleukin-10, and 39 and 625 pg/ml for interleukin-12/interleukin-23 p40. Cytokine concentrations in peripheral blood mononuclear cell supernatants were measured, and results obtained by the microsphere assay were correlated with values obtained with commercially available ELISA kits. This technology is a convenient and reproducible assay to evaluate domestic cat cytokine responses elicited by a variety of diseases.

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“…suspended in 50 ml of PBS as indicated in legend. Mice mortality was monitored up to 180 h. In certain experiments, 6 or 24 h after infection with PA and/or SA, lung homogenates were prepared as described previously 64 and bacterial loads in the lung were examined by checking bacterial c.f.u. in lung homogenates on LB-agar plate.…”

Section: Methodsmentioning

confidence: 99%

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

et al. 2014

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Young cystic fibrosis (CF) patients' airways are mainly colonized by Staphylococcus aureus, while Pseudomonas aeruginosa predominates in adults. However, the mechanisms behind this infection switch are unclear. Here, we show that levels of type-IIA-secreted phospholipase A2 (sPLA2-IIA, a host enzyme with bactericidal activity) increase in expectorations of CF patients in an age-dependent manner. These levels are sufficient to kill S. aureus, with marginal effects on P. aeruginosa strains. P. aeruginosa laboratory strains and isolates from CF patients induce sPLA2-IIA expression in bronchial epithelial cells from CF patients (these cells are a major source of the enzyme). In an animal model of lung infection, P. aeruginosa induces sPLA2-IIA production that favours S. aureus killing. We suggest that sPLA2-IIA induction by P. aeruginosa contributes to S. aureus eradication in CF airways. Our results indicate that a bacterium can eradicate another bacterium by manipulating the host immunity.

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IL-10 delivery by AAV5 vector attenuates inflammation in mice with pseudomonas pneumonia

Cited by 30 publications

References 63 publications

Mesenchymal Stem Cells Prevent Hydrocephalus After Severe Intraventricular Hemorrhage

Mesenchymal Stem Cells Prevent Hydrocephalus After Severe Intraventricular Hemorrhage

Development and Validation of a Multiplex Microsphere-Based Assay for Detection of Domestic Cat ( Felis catus ) Cytokines

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

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