Inhibition of interleukin-1 (IL-1) and tumor necrosis factor (TNF) production by pyridinyl imidazole compounds is independent of cAMP elevating mechanisms

Kassis, Shouki; Prabhakar, Uma; Lee, J. C.

doi:10.1007/bf01972722

Cited by 14 publications

(5 citation statements)

References 9 publications

(5 reference statements)

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“…Al though in some biological systems IL-1 in creases the level of cytosolic cAMP [18], in some cells IL-1 does not change cAMP levels [19][20][21] or may decrease them [22], In some cases, cAMP modulates or mimics effects of IL-1 [23,24], without mediating them. How ever, other effects of IL-1 seem to be indepen dent of cAMP [25,26], cAMP and IL-1 may even have opposing effects; thus, in human lung fibroblasts cAMP inhibits IL-l-induced IL-6 production [27], In the present study IL-1 had no detectable effect on the concentra tion SP-B mRNA, whereas cAMP significant ly increased SP-B mRNA. It is possible that cAMP is not involved in IL-l-induced upregulation of SP-A mRNA.…”

Section: Discussionmentioning

confidence: 39%

lnterleukin-1α Upregulates the Expression of Surfactant Protein-A in Rabbit Lung Explants

et al. 1997

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Interleukin-1 (IL-1) is an important participant in infectious and inflammatory conditions. Interleukin-1 receptor antagonist (IL-1 ra) prevents the effect of IL-1. We have shown that injection of interleukin-1 α (IL-1α) into the amniotic fluid of pregnant rabbits stimulates the expression of surfactant protein-A (SP-A) in the lungs of the fetuses. We hypothesized that IL-1α similarly enhances the expression of SP-A in rabbit lung explants in vitro. Explants obtained from 22-day fetal rabbit lungs were cultured in Waymouth’s medium on a rotating platform in the presence or absence of IL-1α (5.7–570 ng/ml) or IL-Ira (1–10 μg/ml). Dibutyryl cAMP (1 mM) served as a positive control. After 3 days in culture, the explants were harvested and Northern analysis of SP-A was performed using the 1.9-kb rabbit SP-A cDNA probe. IL-1α and dibutyryl cAMP increased the expression of SP-A twofold, as judged by video densitometry. IL-1ra did not change SP-A expression as compared with controls, suggesting that endogenous IL-1 activity was not responsible for the basal level of SP-A expression in the explants. Dibutyryl cAMP increased the expression of SP-B mRNA, whereas IL-1 α had no effect on SP-B mRNA concentration. We conclude that inflammatory mediators interact with lung cells to alter synthesis of important components of the surfactant system.

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Section: Discussionmentioning

confidence: 39%

lnterleukin-1α Upregulates the Expression of Surfactant Protein-A in Rabbit Lung Explants

et al. 1997

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“…Recently, a new class of compounds, cytokine suppressive anti-inflammatory drugs, have been devel oped which are potent inhibitors of TNF-a and IL-l13 production (Young et aI., 1993(Young et aI., , 1997Lee et aI., 1993Lee et aI., , 1994Lee et aI., , 1996Kassis and Prabhakar 1993;Kumar et aI., 1997). Interestingly, these pyridinyl imidazole drugs have been shown to block translation of both TNF-a and IL-l13 by mechanisms independent of cAMP.…”

Section: Mitogen-activated Protein Kinases: Amentioning

confidence: 99%

Inflammatory Mediators and Stroke: New Opportunities for Novel Therapeutics

Barone

Feuerstein

1999

J Cereb Blood Flow Metab

862

610

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Contrary to previous dogmas, it is now well established that brain cells can produce cytokines and chemokines, and can express adhesion molecules that enable an in situ inflammatory reaction. The accumulation of neutrophils early after brain injury is believed to contribute to the degree of brain tissue loss. Support for this hypothesis has been drawn from many studies where neutrophil-depletion blockade of endothelial-leukocyte interactions has been achieved by various techniques. The inflammation reaction is an attractive pharmacologic opportunity, considering its rapid initiation and progression over many hours after stroke and its contribution to evolution of tissue injury. While the expression of inflammatory cytokines that may contribute to ischemic injury has been repeatedly demonstrated, cytokines may also provide “neuroprotection” in certain conditions by promoting growth, repair, and ultimately, enhanced functional recovery. Significant additional basic work is required to understand the dynamic, complex, and time-dependent destructive and protective processes associated with inflammation mediators produced after brain injury. The realization that brain ischemia and trauma elicit robust inflammation in the brain provides fertile ground for discovery of novel therapeutic agents for stroke and neurotrauma. Inhibition of the mitogen-activated protein kinase (MAPK) cascade via cytokine suppressive anti-inflammatory drugs, which block p38 MAPK and hence the production of interleukin-1 and tumor necrosis factor-α, are most promising new opportunities. However, spatial and temporal considerations need to be exercised to elucidate the best opportunities for selective inhibitors for specific inflammatory mediators.

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“…Recently, a new class (entitled CSAID TM compounds: cytokine-suppressive anti-inflammatory drugs) of translational inhibitors of TNF· production has been developed [145,146]. Interestingly, these pyridinyl imidazole drugs have been shown to hamper translation of both TNF· and IL-1ß by mechanisms independent of cAMP involvement.…”

Section: New Strategies For the Treatment Of Brain Injurymentioning

confidence: 99%

The Role of Cytokines in the Neuropathology of Stroke and Neurotrauma

Feuerstein

Wang

Barone³

1998

Neuroimmunomodulation

207

147

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Accumulating evidence during the last decade has shown that the CNS can mount a well-defined inflammatory reaction to a variety of insults including trauma, ischemia, transplantation, viral infections as well as neurodegeneration. Many aspects of this centrally derived inflammatory response parallel to some extent the nature of such a reaction in the periphery. Through the recent application of molecular genetic techniques including PCR, utilization of cDNA probes in conjuncture with the availability of highly specific antibodies, new concepts are rapidly emerging as to the molecular mechanisms associated with the development of brain injury. In particular, the importance of cytokines, especially TNFα and IL-1β, is emphasized in the propagation and maintenance of a CNS inflammatory response. This review summarizes evidence in support of a case for ischemia and trauma eliciting an inflammatory condition in the injured brain. The inflammatory condition consists of cells (neutrophils early after the onset of brain injury and subsequently monocyte infiltration) and mediators (cytokines, chemokines and adhesion molecules). It is clear that de novo up-regulation of pro-inflammatory cytokines, chemokines and endothelial-leukocyte adhesion molecules in the brain occurs soon following focal ischemia and trauma and at a time when the tissue injury is evolving. The significance of the inflammatory response and its contribution to brain injury are now becoming better understood. Evidence has emerged in support of the role of cytokines in driving the inflammatory response and that this process is causally related to the degree of brain injury. Evidence reviewed includes: (1) the capacity of specific cytokines to exacerbate brain damage; (2) the capacity of specific cytokine blockade to reduce ischemic brain damage; (3) depletion of circulating neutrophils reduces ischemic brain injury, and (4) antagonists of the endothelial-leukocyte adhesion interactions (e.g. anti-ICAM-1) reduce ischemic brain injury. Targeting the cytokines that drive the brain inflammatory response to injury provides opportunities to intervene with novel therapeutics in stroke and neurotrauma.

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Inhibition of interleukin-1 (IL-1) and tumor necrosis factor (TNF) production by pyridinyl imidazole compounds is independent of cAMP elevating mechanisms

Cited by 14 publications

References 9 publications

lnterleukin-1α Upregulates the Expression of Surfactant Protein-A in Rabbit Lung Explants

lnterleukin-1α Upregulates the Expression of Surfactant Protein-A in Rabbit Lung Explants

Inflammatory Mediators and Stroke: New Opportunities for Novel Therapeutics

The Role of Cytokines in the Neuropathology of Stroke and Neurotrauma

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