Search

Your search keyword '"Campbell, Iain L."' showing total 716 results
Start Over Author "Campbell, Iain L."
716 results on '"Campbell, Iain L."'

2. Interferon-a receptor antisense oligonucleotides reduce neuroinflammation and neuropathology in a mouse model of cerebral interferonopathy

Author

Viengkhou, Barney, Hong, Christine, Mazur, Curt, Damle, Sagar, Gallo, Nicholas B., Fang, Terry C., Henry, Kate, Campbell, Iain L., Kamme, Fredrik, and Hofer, Markus J.

Subjects
Thermo Fisher Scientific Inc., Cytokines -- Health aspects, Neurons -- Health aspects, Antiviral agents -- Health aspects, Biological response modifiers -- Health aspects, Genetic engineering -- Health aspects, Health care industry
Abstract

Chronic and elevated levels of the antiviral cytokine IFN-[alpha] in the brain are neurotoxic. This is best observed in patients with genetic cerebral interferonopathies such as Aicardi-Goutieres syndrome. Cerebral interferonopathies typically manifest in early childhood and lead to debilitating disease and premature death. There is no cure for these diseases with existing treatments largely aimed at managing symptoms. Thus, an effective therapeutic strategy is urgently needed. Here, we investigated the effect of antisense oligonucleotides targeting the murine IFN- [alpha] receptor (Ifnar1 ASOs) in a transgenic mouse model of cerebral interferonopathy. Intracerebroventricular injection of Ifnar1 ASOs into transgenic mice with brain- targeted chronic IFN-[alpha] production resulted in a blunted cerebral interferon signature, reduced neuroinflammation, restoration of blood-brain barrier integrity, absence of tissue destruction, and lessened neuronal damage. Remarkably, Ifnar1 ASO treatment was also effective when given after the onset of neuropathological changes, as it reversed such disease-related features. We conclude that ASOs targeting the IFN-[alpha] receptor halt and reverse progression of IFN-[alpha]-mediated neuroinflammation and neurotoxicity, opening what we believe to be a new and promising approach for the treatment of patients with cerebral interferonopathies., Introduction Despite the important role type I IFNs like IFN-[alpha] play in the host antiviral immune response, its actions in the central nervous system (CNS) can be debilitating. This is [...]

Published
2024
Full Text
View/download PDF

5. Increased Expression of the Neuropeptides PACAP/VIP in the Brain of Mice with CNS Targeted Production of IL-6 Is Mediated in Part by Trans-Signalling.

Author

Castorina, Alessandro, Scheller, Jurgen, Keay, Kevin A., Marzagalli, Rubina, Rose-John, Stefan, and Campbell, Iain L.

Subjects
PITUITARY adenylate cyclase activating polypeptide, VASOACTIVE intestinal peptide, MESSENGER RNA, CENTRAL nervous system, INTERLEUKIN-6
Abstract

Inflammation with expression of interleukin 6 (IL-6) in the central nervous system (CNS) occurs in several neurodegenerative/neuroinflammatory conditions and may cause neurochemical changes to endogenous neuroprotective systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two neuropeptides with well-established protective and anti-inflammatory properties. Yet, whether PACAP and VIP levels are altered in mice with CNS-restricted, astrocyte-targeted production of IL-6 (GFAP-IL6) remains unknown. In this study, PACAP/VIP levels were assessed in the brain of GFAP-IL6 mice. In addition, we utilised bi-genic GFAP-IL6 mice carrying the human sgp130-Fc transgene (termed GFAP-IL6/sgp130Fc mice) to determine whether trans-signalling inhibition rescued PACAP/VIP changes in the CNS. Transcripts and protein levels of PACAP and VIP, as well as their receptors PAC1, VPAC1 and VPAC2, were significantly increased in the cerebrum and cerebellum of GFAP-IL6 mice vs. wild type (WT) littermates. These results were paralleled by a robust activation of the JAK/STAT3, NF-κB and ERK1/2MAPK pathways in GFAP-IL6 mice. In contrast, co-expression of sgp130Fc in GFAP-IL6/sgp130Fc mice reduced VIP expression and activation of STAT3 and NF-κB pathways, but it failed to rescue PACAP, PACAP/VIP receptors and Erk1/2MAPK phosphorylation. We conclude that forced expression of IL-6 in astrocytes induces the activation of the PACAP/VIP neuropeptide system in the brain, which is only partly modulated upon IL-6 trans-signalling inhibition. Increased expression of PACAP/VIP neuropeptides and receptors may represent a homeostatic response of the CNS to an uncontrolled IL-6 synthesis and its neuroinflammatory consequences. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

15. Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature

Author

Kavanagh, David, McGlasson, Sarah, Jury, Alexa, Williams, Jac, Scolding, Neil, Bellamy, Chris, Gunther, Claudia, Ritchie, Diane, Gale, Daniel P., Kanwar, Yashpal S., Challis, Rachel, Buist, Holly, Overell, James, Weller, Belinda, Flossmann, Oliver, Blunden, Mark, Meyer, Eric P., Krucker, Thomas, Evans, Stephen J.W., Campbell, Iain L., Jackson, Andrew P., Chandran, Siddharthan, and Hunt, David P.J.

Published
2016
Full Text
View/download PDF

19. Blocking Chemokine Responsive to γ–2/Interferon (IFN)-γ Inducible Protein and Monokine Induced by IFN-γ Activity In Vivo Reduces the Pathogenetic but not the Antiviral Potential of Hepatitis B Virus–specific Cytotoxic T Lymphocytes

Author

Kakimi, Kazuhiro, Lane, Thomas E, Wieland, Stefan, Asensio, Valerie C, Campbell, Iain L, Chisari, Francis V, and Guidotti, Luca G

Subjects
Hepatitis, Hepatitis - B, Infectious Diseases, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Liver Disease, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, 5.2 Cellular and gene therapies, Aetiology, Inflammatory and immune system, Infection, Good Health and Well Being, Animals, Chemokine CXCL10, Cytotoxicity, Immunologic, Hepatitis B, Hepatitis B virus, Interferon-gamma, Liver, Mice, Mice, Transgenic, Monokines, T-Lymphocytes, Cytotoxic, chemokines, hepatitis B virus, infectious immunity-virus, liver, Medical and Health Sciences, Immunology
Abstract

Using transgenic mice that replicate hepatitis B virus (HBV) at high levels in the liver as recipients of HBV-specific cytotoxic T lymphocytes (CTLs), we showed that the chemokines responsive to gamma-2/IFN-gamma inducible protein ([Crg2]IP-10) and monokine induced by interferon-gamma (Mig) are rapidly and strongly induced in the liver after CTL transfer. The transferred CTLs produce neither chemokine; rather, they activate (via the secretion of IFN-gamma) hepatocytes and nonparenchymal cells of the liver to produce (Crg2)IP-10 and Mig. Importantly, blocking these chemokines in vivo reduces the recruitment of host-derived lymphomononuclear cells into the liver and the severity of the liver disease without affecting the IFN-gamma-dependent antiviral potential of the CTLs. The finding that neutralization of these chemokines is associated with maintenance of antiviral effects but diminished tissue damage may be significant for the development of immunotherapeutic approaches for the treatment of chronic HBV infection.

Published
2001

22. C

Author

Davis, Justin R., Giles, Andrew C., Rankin, Catharine H., Bell, Jonathan, Kimura, Hiroshi, Uemura, Tadashi, Kidokoro, Yoshi, Lemieux, Mado, Koninck, Paul De, Carbone, Emilio, Senatore, Adriano, Spafford, J. David, Dowie, Megan J., Grimsey, Natasha L., Glass, Michelle, Gillis, Kevin D., Hunter, Peter, Budgell, Brian, Roy, Arijit, Wilson, Richard J. A., Hikosaka, Okihide, Esfeld, Michael, Harbecke, Jens, Mitsuhashi, Takayuki, Takahashi, Takao, Kageyama, Ryoichiro, Ohsawa, Ryosuke, Ohtsuka, Toshiyuki, Lalley, Peter M., Nitabach, Michael N., Paton, Julian F. R., Waitzman, David M., Nattie, Eugene, Li, Aihua, Tsunoda, Ikuo, Kobayashi-Warren, Mikako, Libbey, Jane E., Fujinami, Robert S., Kulkarni, Amod P., Kellaway, Laurie A., Kotwal, Girish J., Morgen, Katrin E., Ciufolini, Maria Grazia, Nicoletti, Loredana, Davis, Randall L., Hofer, Markus J., Campbell, Iain L., Jensen, Troels S., Finnerup, Nanna B., Straub, Volko A., Benarroch, Eduardo E., Bronstein, Adolfo M., Nissant, Antoine, Bloedel, James R., Bracha, Vlastislav, Highstein, Stephen M., Scudder, Charles A., Kachur, Torah M., Pilgrim, Dave B., André, Holley, Mindell, Joseph A., Maduke, Merritt, Ormond, John, Woodin, Melanie A., Datta, Subimal, Eisenstat, David D., Severinsen, Kaare, Jakobsen, Johannes, Merrow, Martha, Roenneberg, Till, Schall, Jeffrey D., Vogt, Brent A., Morecraft, Robert J., Tischkau, Shelley, Gerkema, Menno P., Buijs, Ruud M., Lewy, Alfred J., Hazlerigg, David, Yamamoto, Takashi, Epstein, Marcelo, Ripperger, Jürgen A., Albrecht, Urs, Kramer, Achim, Ruggero, Mario A., Shannon, Robert V., Malmierca, Manuel S., Smith, Philip H., Sodian, Beate, Nieder, Andreas, Mast, Fred W., Godde, Ben, Hansen, Thorsten, Gegenfurtner, Karl R., Faure, Philippe, Allan, Douglas W., Asoh, Hideki, Jänig, Wilfrid, Rybak, Ilya A., Smith, Jeffrey C., Karniel, Amir, Sanguineti, Vittorio, Mansergh, Fiona, R.Wolpaw, Jonathan, McFarland, Dennis J., Mareschal, Denis, Althaus, Nadja, Lee, Tai Sing, Cleland, Thomas A., Goodwin, Graham C., Feuer, Arie, Latash, Mark L., Marín, Oscar, Lucassen, Paul J., Boekhoorn, Karin, Francis, Fiona, Groenewegen, Henk J., Ogawa, Hisashi, Macefield, Vaughan G, Birznieks, Ingvars, Biel, Martin, Binder, Marc D., editor, Hirokawa, Nobutaka, editor, and Windhorst, Uwe, editor

Published
2009
Full Text
View/download PDF

38. Additional file 7 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease

Author

Spiteri, Alanna G., Terry, Rachel L., Wishart, Claire L., Ashhurst, Thomas M., Campbell, Iain L., Hofer, Markus J., and King, Nicholas J. C.

Subjects
nervous system, animal diseases, sense organs
Abstract

Additional file 7 Four microglia phenotypes identified in the homeostatic and infected brain have differential immune profiles. Histograms showing the expression of selected markers on/in P2RY12hiCD86+ (dark purple), P2RY12loCD86- (light green), P2RY12loCD86+ (light purple) and P2RY12hiCD86- (dark green) microglia at dpi 0 (blue) and dpi 7 (orange).

Published
2021
Full Text
View/download PDF

39. Additional file 2 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease

Author

Spiteri, Alanna G., Terry, Rachel L., Wishart, Claire L., Ashhurst, Thomas M., Campbell, Iain L., Hofer, Markus J., and King, Nicholas J. C.

Subjects
animal diseases, virus diseases
Abstract

Additional file 2 Overlapping expression of 'infiltrating macrophage' markers on resident and infiltrating myeloid populations in WNV-infected brains. a-e Histograms and FACs plots showing the expression of CD44 (a), LFA1 (CD11a) (b), VLA4 (CD49d) (c), Ly6C (d) and CCR2 (e) on microglia from homeostatic (blue) and infected (green) brains relative to infiltrating microglia-like (orange) and Ly6Chi macrophages (dark pink) in WNV dpi 7 brains.

Published
2021
Full Text
View/download PDF

41. Additional file 12 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease

Author

Spiteri, Alanna G., Terry, Rachel L., Wishart, Claire L., Ashhurst, Thomas M., Campbell, Iain L., Hofer, Markus J., and King, Nicholas J. C.

Subjects
animal diseases, viruses, virus diseases, nervous system diseases
Abstract

Additional file 12 IL-23 is under the detection threshold in WNV infected brains. Quantity of IL-23 (p19/p40) in mock and WNV-infected mice at dpi 7, as determined using an ELISA.

Published
2021
Full Text
View/download PDF

43. Additional file 8 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease

Author

Spiteri, Alanna G., Terry, Rachel L., Wishart, Claire L., Ashhurst, Thomas M., Campbell, Iain L., Hofer, Markus J., and King, Nicholas J. C.

Subjects
viruses, animal diseases, virus diseases
Abstract

Additional file 8 ‘Microglia-specific’ marker TMEM119 is expressed by infiltrating macrophages populations in the brain but not in the bone marrow or blood. a, b Histograms showing the expression of TMEM119 on microglia (a) in naïve and WNV-infected mice and on microglia, Ly6Chi macrophages and microglia-like macrophages (b) in WNV dpi 7 brains. Fluorescence minus one (FMO) and single stains (ss) for TMEM119 are shown each plot. c-f tSNE plot clustered on live cells from naïve and WNV dpi 7 brains. c, d Annotation of populations found in the mock-infected (c) and infected (d) brain tSNE. e, f Relative expression TMEM119 on tSNE plots representing naïve (e) and WNV-dpi 7 (f) brains. g Heatmap showing the expression TMEM119 on neutrophils, microglia, microglia-like macrophages and Ly6Chi macrophages from four brain samples (1-4). h Expression of TMEM119 on peripheral bone marrow and blood Ly6Chi monocytes and Ly6Chi macrophages in WNV dpi 7 brains. i-k tSNE plot clustered on live, SSC-Alo and Ly6G+/- bone marrow, live, SSC-Alo and Ly6G+/- blood cells and live brain cells from WNV dpi 7 brains. Data is representative of at least two independent experiments, with a minimum 7 animals per group.

Published
2021
Full Text
View/download PDF

44. Additional file 3 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease

Author

Spiteri, Alanna G., Terry, Rachel L., Wishart, Claire L., Ashhurst, Thomas M., Campbell, Iain L., Hofer, Markus J., and King, Nicholas J. C.

Abstract

Additional file 3 Microglia are easily identifiable in the homoeostatic brain. a-d Quality control gates, including time (a), single cells (b), non-debris (c) and live cell (d) gates were applied before analysing cells. Neutrophils were also excluded by their expression of Ly6G (e). f Gating strategy one identifies a ‘resting’ microglia population (CD45lo CD11b+) (R1: blue) and an ‘activated’ microglia population (CD45int CD11b+) (R2: red). h, j Gating strategy two, does not use ‘microglia-specific markers’ and identifies microglia as CX3CR1+ CD45lo-int CD11b+ Ly6C-/lo. Gating strategy three is a revised gating strategy which identifies microglia as CX3CR1+ CD45lo-int CD11b+ P2RY12+ Ly6C-/lo (h, I, l). n, o Gating strategy four uses a limited number of markers and identifies microglia as CD45lo-int P2RY12+CD11b+CX3CR1+. g, k, m, p ‘Microglia’ populations gated using strategies 1 (g), 2 (k), 3 (m), and 4 (p), overlaid onto a tSNE plot, clustered on live cells from mock-infected brains. q, r Number (q) and frequency (r) of ‘microglia’ gated using strategies 1-4. Data is presented as mean ± SEM, from two independent experiments with at least six mice per group. **P

Published
2021
Full Text
View/download PDF

45. Additional file 5 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease

Author

Spiteri, Alanna G., Terry, Rachel L., Wishart, Claire L., Ashhurst, Thomas M., Campbell, Iain L., Hofer, Markus J., and King, Nicholas J. C.

Subjects
viruses, animal diseases, parasitic diseases, virus diseases, biochemical phenomena, metabolism, and nutrition
Abstract

Additional file 5 Immune profiles of resident microglia and infiltrating myeloid cells in WNE at dpi 7.

Published
2021
Full Text
View/download PDF

46. Additional file 9 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease

Author

Spiteri, Alanna G., Terry, Rachel L., Wishart, Claire L., Ashhurst, Thomas M., Campbell, Iain L., Hofer, Markus J., and King, Nicholas J. C.

Subjects
viruses, animal diseases, virus diseases
Abstract

Additional file 9 ‘Microglia-specific’ marker P2RY12 is expressed by infiltrating macrophages populations in the brain but not in the bone marrow or blood. a, b Histograms showing the expression of P2RY12 on microglia (a) in naïve and WNV-infected mice and on microglia, Ly6Chi macrophages and microglia-like macrophages (b) in WNV dpi 7 brains. Fluorescence minus one (FMO) and single stains (ss) for P2RY12 are shown each plot. c-f tSNE plot clustered on live cells from naïve and WNV dpi 7 brains. c, d Annotation of populations found in the mock-infected (c) and infected (d) brain tSNE. e, f Relative expression P2RY12 on tSNE plots representing naïve (e) and WNV-dpi 7 (f) brains. g Heatmap showing the expression P2RY12 on neutrophils, microglia, microglia-like macrophages and Ly6Chi macrophages from four brain samples (1-4). h Expression of P2RY12 on peripheral bone marrow and blood Ly6Chi monocytes and Ly6Chi macrophages in WNV dpi 7 brains. i-k tSNE plot clustered on live, SSC-Alo and Ly6G+/- bone marrow, live, SSC-Alo and Ly6G+/- blood cells and live brain cells from WNV dpi 7 brains. Data is representative of at least two independent experiments, with a minimum 7 animals per group.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results