Controlling cytokine signaling by constitutive inhibitors

Rakesh, Kriti; Agrawal, Devendra K.

doi:10.1016/j.bcp.2005.04.042

Cited by 108 publications

(87 citation statements)

References 48 publications

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“…In addition to the neuroprotective actions of SOCS1 and SOCS3 by 15d-PGJ2 and rosiglitazone, two other family of proteins, the SH2-containing phospatases (SHPs) and the protein inhibitors of activated STATs (PIAS) act cooperatively with the SOCS proteins to inhibit cytokine overproduction (67,73). Park et al (67) proposed that SHP activation in microglia might be directly related to attenuated brain inflammation.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists

Kapadia

Yi²,

Vemuganti³

2008

Front Biosci

378

246

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Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. The 3 PPAR isoforms (alpha, delta/beta and gamma) are known to control many physiological functions including glucose absorption, lipid balance, and cell growth and differentiation. Of interest, PPAR-gamma activation was recently shown to mitigate the inflammation associated with chronic and acute neurological insults. Particular attention was paid to test the therapeutic potential of PPAR agonists in acute conditions like stroke, spinal cord injury (SCI) and traumatic brain injury (TBI), in which massive inflammation plays a detrimental role. While 15d-prostaglandin J2 (15d PGJ 2 ) is the natural ligand of PPAR-gamma, the thiazolidinediones (TZDs) are potent exogenous agonists. Due to their insulin-sensitizing properties, 2 TZDs rosiglitazone and pioglitazone are currently FDA-approved for type-2 diabetes treatment. Recent studies from our laboratory and other groups have shown that TZDs induce significant neuroprotection in animal models of focal ischemia and SCI by multiple mechanisms. The beneficial actions of TZDs were observed to be both PPAR-gamma-dependent as well as -independent. The major mechanism of TZD-induced neuroprotection seems to be prevention of microglial activation and inflammatory cytokine and chemokine expression. TZDs were also shown to prevent the activation of pro-inflammatory transcription factors at the same time promoting the anti-oxidant mechanisms in the injured CNS. This review article discusses the multiple mechanisms of TZDinduced neuroprotection in various animal models of CNS injury with an emphasis on stroke. KeywordsTranscription Factor; Inflammation; Brain Damage; Nuclear Factor; Cerebral Ischemia; Stroke; Neuroprotection; Review INTRODUCTIONStroke is the leading cause of long-term disability in the adult population worldwide. A variety of pathophysiological processes contribute to the irreversible neuronal injury that eventually results in neurological dysfunction after stroke. The complex nature of these processes involves specific cell types that effect several downstream signalling pathways. In a majority of stroke patients, only a small area of the brain tissue, the ischemic core, is irreversibly damaged. A much larger volume of the brain tissue surrounding the ischemic core, called the penumbra, can potentially recover if treatment is provided in a timely manner (3). Tissue protection and regeneration are tightly regulated by cell growth, survival and cell death signals provided by the cellular microenvironment. Hence, understanding the molecular mechanisms that govern Send correspondence to: Dr. Raghu Vemuganti, Department of Neurological Surgery, K4/8 Mail code CSC 8660, 600 Highland Avenue, Madison, WI 53792, Tel:608-263-4055, Fax:608-263-1728, E-mail: vemugant@neurosurg.wisc.edu. NIH Public Access Author ManuscriptFront Biosci. Author manuscript; available in PMC 2009 August 28. Published in final edited form as:Fr...

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Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists

Kapadia

Yi²,

Vemuganti³

2008

Front Biosci

378

246

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“…Protein tyrosine phosphatases act in both the cytoplasm and nucleus to inhibit target protein phosphorylation events. STAT-3 signaling is dampened by protein tyrosine phosphatases, such as the SH2-domain containing tyrosine phosphatase family (SHP-1 and SHP-2), which down-regulate STAT-3 activation directly by dephosphorylating active STAT-3 complexes (15).…”

Section: Stat-3 Inhibition By Pias Proteins and Protein Tyrosine Phosmentioning

confidence: 99%

“…In addition to targeting STAT-3 for pharmacologic inhibition, recent studies have focused on enhancing endogenous cellular mechanisms for modulating STAT-3 activity, namely, the inhibitory pathways involving PIAS3, SOCS-3, and protein tyrosine phosphatases (15).…”

Section: Endogenous Negative Regulation By Pias3mentioning

confidence: 99%

Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas

Brantley

Benveniste

2008

Molecular Cancer Research

212

159

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“…Among predicted targets, we found one which can be directly related to cytokine signaling, SOCS1 (suppressor of cytokine signaling). Loss of function of this protein is involved in the development and progression of several specific cancers, because SOCS1 exerts the function of a negative feedback regulator of STAT action, and the latter is involved in cellular processes including proliferation, cell survival and angiogenesis (19). Constitutive activation of the STAT indicating altered JAK/STAT signaling has been reported for several lymphomas including classical Hodgkin's lymphoma and primary mediastinal Bcell lymphoma (20).…”

Section: Introductionmentioning

confidence: 99%

miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia

Zanette¹,

Rivadavia²,

Molfetta³

et al. 2007

Braz J Med Biol Res

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MicroRNAs (miRNAs) are a class of small endogenous RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their association with cancer. We determined the miRNA expression profile of chronic and acute lymphocytic leukemias (CLL and ALL) using the TaqMan ® MicroRNA Assays Human Panel (Applied Biosystems). Pooled leukemia samples were compared to pooled CD19 + samples from healthy individuals (calibrator) by the 2 -∆∆Ct method. Total RNA input was normalized based on the Ct values obtained for hsa-miR-30b. The five most highly expressed miRNAs were miR-128b, miR-204, miR-218, miR-331, and miR181b-1 in ALL, and miR-331, miR-29a, miR-195, miR-34a, and miR29c in CLL. To our knowledge, this is the first report associating miR128b, miR-204 and miR-331 to hematological malignancies. The miR-17-92 cluster was also found to be up-regulated in ALL, as previously reported for some types of lymphomas. The differences observed in gene expression levels were validated for miR-331 and miR-128b in ALL and CD19 + samples. These miRNAs were upregulated in ALL, in agreement with our initial results. A brief target analysis was performed for miR-331. One of its putative targets, SOCS1, promotes STAT activation, which is a known mediator of cell proliferation and survival, suggesting the possibility of an association between miR-331 and these processes. This initial screening provided information on miRNA differentially expressed in normal and malignant B-cells that could suggest the potential roles of these miRNAs in hematopoiesis and leukemogenesis.

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Controlling cytokine signaling by constitutive inhibitors

Cited by 108 publications

References 48 publications

Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists

Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists

Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas

miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia

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