Role of ERK MAP kinases in responses of cultured human airway smooth muscle cells to IL-1β

Laporte, Johanne D.; Moore, Paul; Abraham, Joseph H.; Maksym, Geoffrey N.; Fabry, Ben; Panettieri, Reynold A.; Shore, Stephanie A.

doi:10.1152/ajplung.1999.277.5.l943

Cited by 52 publications

(80 citation statements)

References 41 publications

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“…Thus, activation of NF-κB and MAP kinase pathways by hypertonicity may be initiated by the same stimulus. MAP kinase activation by cytokines also upregulates COX2 expression by mechanisms independent of NF-κB (15,16,42,43). This latter effect may account for the residual induction of COX2 by hypertonicity after blocking NF-κB activity (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

Dehydration activates an NF-κB–driven, COX2-dependent survival mechanism in renal medullary interstitial cells

Hao¹,

Yull²,

Blackwell³

et al. 2000

J. Clin. Invest.

137

157

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Renal prostaglandin (PG) synthesis is mediated by cyclooxygenase-1 and -2 (COX1 and COX2). After dehydration, the maintenance of normal renal function becomes particularly dependent upon PG synthesis. The present studies were designed to examine the potential link between medullary COX1 and COX2 expression in hypertonic stress. In response to water deprivation, COX2, but not COX1, mRNA levels increase significantly in the renal medulla, specifically in renal medullary interstitial cells (RMICs). Water deprivation also increases renal NF-κB-driven reporter expression in transgenic mice. NF-κB activity and COX2 expression could be induced in cultured RMICs with hypertonic sodium chloride and mannitol, but not urea. RMIC COX2 expression was also induced by driving NF-κB activation with a constitutively active IκB kinase α (IKKα). Conversely, introduction of a dominant-negative IκB mutant reduced COX2 expression after hypertonicity or IKKα induction. RMICs failed to survive hypertonicity when COX2 was downregulated using a COX2-selective antisense or blocked with the selective nonsteroidal anti-inflammatory drug (NSAID) SC58236, reagents that did not affect cell survival in isotonic media. In rabbits treated with SC58236, water deprivation induced apoptosis of medullary interstitial cells in the renal papilla. These results demonstrate that water deprivation and hypertonicity activate NF-κB. The consequent increase in COX2 expression favors RMIC survival in hypertonic conditions. Inhibition of RMIC COX2 could contribute to NSAID-induced papillary injury.

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Section: Discussionmentioning

confidence: 99%

Dehydration activates an NF-κB–driven, COX2-dependent survival mechanism in renal medullary interstitial cells

Hao¹,

Yull²,

Blackwell³

et al. 2000

J. Clin. Invest.

137

157

View full text Add to dashboard Cite

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“…Stimulation with IL-1b for 15 minutes dramatically increased the phosphorylation of ERK. The choice of this time point was based on previous observations (51). The increased phosphorylation of ERK was not blocked by pretreatment with either troglitazone or rosiglitazone.…”

Section: Role Of Erk and Nf-kbmentioning

confidence: 99%

Anti-inflammatory Effects of Thiazolidinediones in Human Airway Smooth Muscle Cells

Zhu¹,

Flynt

Ghosh

et al. 2011

Am J Respir Cell Mol Biol

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Airway smooth muscle (ASM) cells have been reported to contribute to the inflammation of asthma. Because the thiazolidinediones (TZDs) exert anti-inflammatory effects, we examined the effects of troglitazone and rosiglitazone on the release of inflammatory moieties from cultured human ASM cells. Troglitazone dosedependently reduced the IL-1b-induced release of IL-6 and vascular endothelial growth factor, the TNF-a-induced release of eotaxin and regulated on activation, normal T expressed and secreted (RANTES), and the IL-4-induced release of eotaxin. Rosiglitazone also inhibited the TNF-a-stimulated release of RANTES. Although TZDs are known to activate peroxisome proliferator-activated receptor-g (PPARg), these anti-inflammatory effects were not affected by a specific PPARg inhibitor (GW 9662) or by the knockdown of PPARg using short hairpin RNA. Troglitazone and rosiglitazone each caused the activation of adenosine monophosphate-activated protein kinase (AMPK), as detected by Western blotting using a phospho-AMPK antibody. The anti-inflammatory effects of TZDs were largely mimicked by the AMPK activators, 5-amino-4-imidazolecarboxamide ribose (AICAR) and metformin. However, the AMPK inhibitors, Ara A and Compound C, were not effective in preventing the antiinflammatory effects of troglitazone or rosiglitzone, suggesting that the effects of these TZDs are likely not mediated through the activation of AMPK. These data indicate that TZDs inhibit the release of a variety of inflammatory mediators from human ASM cells, suggesting that they may be useful in the treatment of asthma, and the data also indicate that the effects of TZDs are not mediated by PPARg or AMPK.

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“…Inflammation-induced changes in the intrinsic contractility of airway smooth muscle is one of the elements thought to be involved. Techniques have been developed that allow assessment of the micromechanics of human airway smooth muscle cells in culture [47][48][49][50]. This includes the magnetic twisting cytometry.…”

Section: Micromechanics Of Airway Smooth Muscle Cellsmentioning

confidence: 99%

Murine models of asthma

Kips¹,

Anderson²,

Fredberg³

et al. 2003

Eur Respir J

183

123

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In vivo animal models can offer valuable information on several aspects of asthma pathogenesis and treatment. The mouse is increasingly used in these models, mainly because this species allows for the application in vivo of a broad range of immunological tools, including gene deletion technology. Mice, therefore, seem particularly useful to further elucidate factors influencing the response to inhaled allergens. Examples include: the role of immunoregulatory mechanisms that protect against T-helper cell type 2 cell development; the trafficking of T-cells; and the contribution of the innate immunity. However, as for other animal species, murine models also have limitations. Mice do not spontaneously develop asthma and no model mimics the entire asthma phenotype. Instead, mice should be used to model specific traits of the human disease. The present task force report draws attention to specific aspects of lung structure and function that need to be borne in mind when developing such models and interpreting the results. In particular, efforts should be made to develop models that mimic the lung function changes characteristic of asthma as closely as possible. A large section of this report is therefore devoted to an overview of airway function and its measurement in mice.

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Role of ERK MAP kinases in responses of cultured human airway smooth muscle cells to IL-1β

Cited by 52 publications

References 41 publications

Dehydration activates an NF-κB–driven, COX2-dependent survival mechanism in renal medullary interstitial cells

Dehydration activates an NF-κB–driven, COX2-dependent survival mechanism in renal medullary interstitial cells

Anti-inflammatory Effects of Thiazolidinediones in Human Airway Smooth Muscle Cells

Murine models of asthma

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