Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

Strien, Miriam E. van; Mercier, Dominique; Drukarch, Benjamin; Brevé, John; Poole, Stephen; Binnekade, R.; Bol, John G.J.M.; Blits, Bas; Verhaagen, Joost; Dam, A-M. Van

doi:10.1038/gt.2010.8

Cited by 21 publications

(18 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In models of liver fibrosis, macrophage phagocytosis of apoptotic hepatocytes also reduces inflammation and prevents the development of fibrosis (231), and phagocytosis of apoptotic cholangiocytes reverses existing fibrosis (232). A defining marker of regulatory macrophage function is the secretion of IL-10; direct IL-10 treatment, genetically modified or transfused IL-10-stimulated macrophages, or in vivo induction of macrophage IL-10 expression can ameliorate fibrosis and inflammation in kidney, gut, and brain (201, 204, 233–235). Arginase-1-expressing M2 macrophages have also been implicated in the amelioration of liver fibrosis induced by chronic S. mansoni infection (236).…”

Section: The Role Of Monocyte and Macrophage Populations In Fibrosis mentioning

confidence: 99%

Host Responses in Tissue Repair and Fibrosis

Duffield

Lupher

Thannickal

et al. 2013

Annu. Rev. Pathol. Mech. Dis.

539

500

View full text Add to dashboard Cite

Myofibroblasts accumulate in the spaces between organ structures and produce extracellular matrix (ECM) proteins, including collagen I. They are the primary “effector” cells in tissue remodeling and fibrosis. Previously, leukocyte progenitors termed fibrocytes and myofibroblasts generated from epithelial cells through epithelial-to-mesenchymal transition (EMT) were considered the primary sources of ECM-producing myofibroblasts in injured tissues. However, genetic fate mapping experiments suggest that mesenchyme-derived cells, known as resident fibroblasts, and pericytes are the primary precursors of scar-forming myofibroblasts, whereas epithelial cells, endothelial cells, and myeloid leukocytes contribute to fibrogenesis predominantly by producing key fibrogenic cytokines and by promoting cell-to-cell communication. Numerous cytokines derived from T cells, macrophages, and other myeloid cell populations are important drivers of myofibroblast differentiation. Monocyte-derived cell populations are key regulators of the fibrotic process: They act as a brake on the processes driving fibrogenesis, and they dismantle and degrade established fibrosis. We discuss the origins, modes of activation, and fate of myofibroblasts in various important fibrotic diseases and describe how manipulation of macrophage activation could help ameliorate fibrosis.

show abstract

Section: The Role Of Monocyte and Macrophage Populations In Fibrosis mentioning

confidence: 99%

Host Responses in Tissue Repair and Fibrosis

Duffield

Lupher

Thannickal

et al. 2013

Annu. Rev. Pathol. Mech. Dis.

539

500

View full text Add to dashboard Cite

show abstract

“…[37][38][39] As an alternative, lentivirus-derived expression systems have been employed in animal models of neuroinflammation. 40 Lentivectors not only infect dividing and quiescent cells, but they also provide long-term expression and show low immunogenicity. In addition, the biosafety profile of LVs has been improved significantly by minimizing the regions of homology between vector and helper sequences (split configuration), and by using heterologous promoters.…”

Section: Discussionmentioning

confidence: 99%

IL10 Released by a New Inflammation-regulated Lentiviral System Efficiently Attenuates Zymosan-induced Arthritis

et al. 2013

View full text Add to dashboard Cite

“…Plasmid IL-10 mRNA was detected in both the CSF and lumbar spinal cord, and increased the number of CD163+ cells (a marker of M2 activation) in the lumbar spinal cord (Soderquist et al, 2010). Naked pDNA-IL-10 F129S or lentivirally expressed IL-10 previously attenuated motor symptoms and mechanical allodynia in the rat model of relapsing remitting EAE (Sloane et al, 2009; van Strien et al, 2010). Furthermore, naked pDNA-IL-10 F129S decreased GFAP expression (a marker for astrocyte activation) and the number of CD68+ cells (a marker of M1 activation) in the lumbar spinal cord (Sloane et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Behavioral assessment of neuropathic pain, fatigue, and anxiety in experimental autoimmune encephalomyelitis (EAE) and attenuation by interleukin-10 gene therapy

Grace

Loram

Christianson

et al. 2017

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Relapsing-remitting multiple sclerosis is commonly associated with motor impairments, neuropathic pain, fatigue, mood disorders, and decreased life expectancy. However, preclinical pharmacological studies predominantly rely on clinical scoring of motor deficit as the sole behavioral endpoint. Thus, the translational potential of these studies is limited. Here, we have assessed the therapeutic potential of a novel anti-inflammatory interleukin-10 (IL-10) non-viral gene therapy formulation (XT-101-R) in a rat relapsing remitting experimental autoimmune encephalomyelitis (EAE) model. EAE induced motor deficits and neuropathic pain as reflected by induction of low-threshold mechanical allodynia, suppressed voluntary wheel running, decreased social exploration, and was associated with markedly enhanced mortality. We also noted that voluntary wheel running was depressed prior to the onset of motor deficit, and may therefore serve as a predictor of clinical symptoms onset. XT-101-R was intrathecally dosed only once at the onset of motor deficits, and attenuated each of the EAE-induced symptoms and improved survival, relative to vehicle control. This is the first pharmacological assessment of such a broad range of EAE symptoms, and provides support for IL-10 gene therapy as a clinical strategy for the treatment of multiple sclerosis.

show abstract

Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

Cited by 21 publications

References 74 publications

Host Responses in Tissue Repair and Fibrosis

Host Responses in Tissue Repair and Fibrosis

IL10 Released by a New Inflammation-regulated Lentiviral System Efficiently Attenuates Zymosan-induced Arthritis

Behavioral assessment of neuropathic pain, fatigue, and anxiety in experimental autoimmune encephalomyelitis (EAE) and attenuation by interleukin-10 gene therapy

Contact Info

Product

Resources

About