Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice.

Kuruvilla, A P; Shah, Rutvi; Hochwald, G. M.; Liggitt, H. Denny; Palladino, Michael A.; Thorbecke, G. J.

doi:10.1073/pnas.88.7.2918

Cited by 349 publications

(194 citation statements)

References 40 publications

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“…In the CNS, astrocytes, microglia, and oligodendrocytes can be activated to express TGF-␤ (50 -52). In EAE, TGF-␤ expression is prominent during the recovery phase (53) and has been proposed to contribute to disease recovery (54,55). The immunosuppressive function of TGF-␤ on microglia has been reported in our laboratory as well as others.…”

Section: Discussionsupporting

confidence: 54%

Differential Regulation and Function of Fas Expression on Glial Cells

Lee¹,

Zhou

Choi³

et al. 2000

The Journal of Immunology

121

104

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Fas/Apo-1 is a member of the TNF receptor superfamily that signals apoptotic cell death in susceptible target cells. Fas or Fas ligand (FasL)-deficient mice are relatively resistant to the induction of experimental allergic encephalomyelitis, implying the involvement of Fas/FasL in this disease process. We have examined the regulation and function of Fas expression in glial cells (astrocytes and microglia). Fas is constitutively expressed by primary murine microglia at a low level and significantly up-regulated by TNF-α or IFN-γ stimulation. Primary astrocytes express high constitutive levels of Fas, which are not further affected by cytokine treatment. In microglia, Fas expression is regulated at the level of mRNA expression; TNF-α and IFN-γ induced Fas mRNA by ∼20-fold. STAT-1α and NF-κB activation are involved in IFN-γ- or TNF-α-mediated Fas up-regulation in microglia, respectively. The cytokine TGF-β inhibits basal expression of Fas as well as cytokine-mediated Fas expression by microglia. Upon incubation of microglial cells with FasL-expressing cells, ∼20% of cells underwent Fas-mediated cell death, which increased to ∼60% when cells were pretreated with either TNF-α or IFN-γ. TGF-β treatment inhibited Fas-mediated cell death of TNF-α- or IFN-γ-stimulated microglial cells. In contrast, astrocytes are resistant to Fas-mediated cell death, however, ligation of Fas induces expression of the chemokines macrophage inflammatory protein-1β (MIP-1β), MIP-1α, and MIP-2. These data demonstrate that Fas transmits different signals in the two glial cell populations: a cytotoxic signal in microglia and an inflammatory signal in the astrocyte.

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Section: Discussionsupporting

confidence: 54%

Differential Regulation and Function of Fas Expression on Glial Cells

Lee¹,

Zhou

Choi³

et al. 2000

The Journal of Immunology

121

104

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“…29 Our results are also supported in light of the traditional view that TGF-b plays a protective role in matrix metabolism. 30,31 Moreover, TGF-b has been described to inhibit IL1-b-induced chondrocyte protease activity and cartilage proteoglycan degradation, and promote proteoglycan synthesis in cartilage. 32 However, our data point out that the balance between the catabolic versus anabolic stimuli provided by proinflammatory cytokines and TGF-b3, observed in the presence of 1 ng=mL of both cytokines, is unstable.…”

Section: Discussionmentioning

confidence: 99%

ERK1/2 Activation Induced by Inflammatory Cytokines Compromises Effective Host Tissue Integration of Engineered Cartilage

Djouad

Rackwitz

Song

et al. 2009

Tissue Engineering Part A

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“…In mice, microgram amounts of either active or latent protein are required to achieve immunosuppressive effects. 125,126 Recently, several investigators examined gene therapy approaches of delivery. Intramuscular (i.m.)…”

Section: Anti-inflammatory Cytokine Gene Therapymentioning

confidence: 99%