Cytokine-directed therapies for asthma☆☆☆

Barnes, Peter J.

doi:10.1067/mai.2001.116435

Cited by 62 publications

(27 citation statements)

References 66 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most of the strategies aim to block Th2 cell differentiation and the production of Th2 cytokines (37,38). One of the potential strategies is to develop drugs that block the signal transduction pathway required for Th2 cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Ras Activation in T Cells Determines the Development of Antigen-Induced Airway Hyperresponsiveness and Eosinophilic Inflammation

Shibata

Kamata

Kimura

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

The central role for Th2 cells in the development of Ag-induced airway hyperresponsiveness and eosinophilic inflammation is well documented. We have reported a crucial role for TCR-induced activation of the Ras/extracellular signal-regulated kinase mitogen-activated protein kinase cascade in Th2 cell differentiation. Here, we show that the development of both OVA-induced airway hyperresponsiveness and eosinophilic airway inflammation in a mouse asthma model are attenuated in transgenic mice by the overexpression of enzymatically inactive Ras molecules in T cells. In addition, reduced levels of IL-5 production and eosinophilic inflammation induced by nematode infection (Nippostrongylus brasiliensis or Heligmosomoides polygyrus) were detected. Thus, the level of Ras activation in T cells appears to determine Th2-dependent eosinophilic inflammation and Ag-induced airway hyperresponsiveness.

show abstract

Section: Discussionmentioning

confidence: 99%

Ras Activation in T Cells Determines the Development of Antigen-Induced Airway Hyperresponsiveness and Eosinophilic Inflammation

Shibata

Kamata

Kimura

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Increased levels of proinflammatory cytokines in the airways are characteristic of asthma and COPD (9). In human monocytes, the expression of MMP-12 has been reported to be regulated by tumor necrosis factor-α (TNF-α ), which is known as one of the proinflammatory cytokines (10), but the detailed mechanism underlying MMP-12 expression induced by TNF-α in airway epithelial cell is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Possible Involvements of Nuclear Factor-κB and Activator Protein-1 in the Tumor Necrosis Factor-α–Induced Upregulation of Matrix Metalloproteinase-12 in Human Alveolar Epithelial A549 Cell Line

Yu¹,

Chiba²,

Sakai³

et al. 2010

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. Matrix metalloproteinase-12 (MMP-12) has been suggested to play an important role in airway inflammatory diseases. Tumor necrosis factor-α (TNF-α ) is known to cause an upregulation of MMP-12 via an activation of activator protein-1 (AP-1) in monocytes. In the present study, we investigated the effect of TNF-α on the expressions of MMP-12 in airway epithelial cells, one of the sources of MMP-12 in the airway, and its underlying mechanism. MMP-12 mRNA and protein expressions induced by TNF-α in the absence or presence of BMS-345541 (a selective I κ B kinase inhibitor) or SP600125 [a selective c-Jun N-terminal kinase (JNK) inhibitor] were measured by quantitative real-time PCR and Western blotting, respectively. Furthermore, siRNAs for p65 and JNK2 were used to confirm the involvements of nuclear factor-κ B (NF-κ B) and AP-1 in the MMP-12 mRNA expression induced by TNF-α in A549 cells. Both MMP-12 mRNA and protein were upregulated by the treatment with TNF-α in time-and concentration-dependent manners. Both BMS-345541 and SP600125 inhibited the upregulation of MMP-12 induced by TNF-α . Furthermore, both the depletion of p65 and JNK2 by siRNAs significantly attenuated the upregulation of MMP-12 induced by TNF-α . These findings suggest that both NF-κ B and JNK / AP-1 pathways are important for the MMP-12 upregulation induced by TNF-α in A549 cells.Keywords: matrix metalloproteinase-12 (MMP-12), tumor necrosis factor-α (TNF-α ), nuclear factor-κ B (NF-κ B), activator protein-1 (AP-1)Full Paper

show abstract

“…The first line of these immunomodulatory regimens has now passed initial evaluations in clinical trials, and results are not always favourable (73,74). The conclusion one may draw from these study results is that the clinical situation of asthma in humans is clearly more complex than the experimental situation in animal models (75,76). Simply targeting one single cellular or molecular mediator or pathway may not be sufficient to cope with the complex and redundant inflammatory process involved in the development of human asthma (77).…”

Section: Discussionmentioning

confidence: 99%