Cytokine and chemokine expression in cigarette smoke-induced lung injury in guinea pigs

Kubo, Satoshi

doi:10.1183/09031936.05.00042405

Cited by 59 publications

(45 citation statements)

References 36 publications

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“…On the basis of a literature search, we chose one gene that is reported to be increased by TS exposure in airway epithelium (IL-8) and one gene that is suppressed by TS exposure (eotaxin) (10,13). The results from our bioinformatics approach were combined with our array results (Table 1) to develop a schematic representation of the predicted TS-regulated TF binding sites present on IL-8 and eotaxin (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells

Zhao¹,

Harper²,

Barchowsky³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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May 11, 2007; doi:10.1152/ajplung.00345.2006.-Activation and regulation of transcription factors (TFs) are the major mechanisms regulating changes in gene expression upon environmental exposure. Tobacco smoke (TS) is a complex mixture of chemicals, each of which could act through different signal cascades, leading to the regulation of distinct TFs and alterations in subsequent gene expression. We proposed that TS exposure affects inflammatory gene expression at the transcriptional level by modulating the DNA binding activities of TFs. To investigate transcriptional regulation upon TS exposure, a protein/ DNA array was applied to screen TFs that are affected by TS exposure. This array-based screening allowed us to simultaneously detect 244 different TFs. Our results indicated that multiple TFs were rapidly activated upon TS exposure. DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our results showed that at least 20 TFs displayed more than twofold expressional changes after smoke treatment. Ten smoke-induced TFs, including NF-B, VDR, ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-B family, which is involved in inflammation-induced gene activation, was selected for further study to characterize TS exposure-induced transcriptional activation. Western blot analysis and immunofluorescence microscopy indicated that TS exposure induced phosphorylation of IB and translocation of NF-B p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK signaling pathways by TS exposure increased transcriptional activity of NF-B. These data provide a potential mechanism for TS-induced inflammatory gene expression. tobacco smoke; transcription factor; MAPK; NF-B TRANSCRIPTIONAL ACTIVATION in eukaryotes is a highly regulated process that requires the concerted interactions of DNA-binding transcriptional activators, general transcription factors (TFs), and coactivator proteins to stimulate the recruitment and activity of RNA polymerase II to the appropriate gene promoters in response to biological signals. Most of these signals are generated by extracellular signaling molecules that initiate distinct signaling pathways, consequently terminating in the activation of one or more TFs. Abnormalities in signal transduction and TF activation underlie several inflammatory diseases and the majority of cancers (3, 4). Specifically, chronic inflammatory airway diseases and lung cancer are frequently associated with tobacco smoke (TS) exposure, consistent with the high volume of TS to which the lungs are exposed. However, the molecular mechanisms underlying TS-induced pulmonary diseases are not well understood. To better characterize the mechanisms responsible for TS-induced lung diseases, our initial approach was to investigate TS-regulated TF activation in airway epithelial cells and the potential upstream signaling pathways responsible for this upregulation.TS is a chemical mixture that contains mor...

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Section: Discussionmentioning

confidence: 99%

Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells

Zhao¹,

Harper²,

Barchowsky³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Rather, a constant volume, 35 mL of each sample was subjected to 10% sodium dodecyl sulfate (SDS)-polyacrylamide gel elecrophoresis (PAGE) under nonreducing conditions and then proteins were transferred to polyvinyl difluoride membranes (Bio-Rad). This then allowed comparison of the intensity of the final bands in a manner similar to immunoassay [21,22]. After blocking with 5% nonfat milk, blots were incubated overnight at 4uC with primary antibodies (1 mg?mL -1 mouse anti-human MMP-1 or MMP-3 monoclonal antibody).…”

Section: Western Blot Analysis Of Metalloproteinasementioning

confidence: 99%

Statins inhibit matrix metalloproteinase release from human lung fibroblasts

et al. 2009

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Pleiotropic effects of statins have been reported to include inhibition of matrix metalloproteinase (MMP) release from macrophages and endothelial cells. We evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodelling processes.Monolayer and three-dimensional (3D) collagen gel cultures of fibroblasts were used. Cytokines (tumour necrosis factor-a and interleukin-1a) were used to induce MMP release and mRNA expression. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Atorvastatin inhibited MMP-1 and -3 release and mRNA expression in both culture systems. Similar results were obtained with simvastatin and fluvastatin.In 3D cultures where cytokines also stimulated MMP-9 release, atorvastatin also inhibited MMP-9 release. In 3D cultures, cytokines together with NE induced collagen degradation, which was also inhibited by atorvastatin. The effect of atorvastatin was reversed by mevalonate and geranylgeranyl-pyrophosphate but not by farnesyl-pyrophosphate.The current data suggest that statins may modulate remodelling processes mediated by fibroblasts by inhibiting MMP release.

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“…But the pathology of cigarette smoke exposure is similar in guinea pigs and humans. Features of the cigarette smoke-exposed lung of guinea pigs similar to that seen in COPD include an acute neutrophilia, a slowly developing but sustained recruitment of monocytes, alveolar destruction, mucus secretion, increased epithelial permeability, altered reflexes and pulmonary hypertension [209][210][211][212][213][214][215][216][217][218][219].…”

Section: Cigarette Smokementioning

confidence: 99%

Using guinea pigs in studies relevant to asthma and COPD

Canning

Chou

2008

Pulmonary Pharmacology & Therapeutics

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The guinea pig has been the most commonly used small animal species in preclinical studies related to asthma and COPD. The primary advantages of the guinea pig are the similar potencies and efficacies of agonists and antagonists in human and guinea pig airways and the many similarities in physiological processes, especially airway autonomic control and the response to allergen. The primary disadvantages to using guinea pigs are the lack of transgenic methods, limited numbers of guinea pig strains for comparative studies and a prominent axon reflex that is unlikely to be present in human airways. These attributes and various models developed in guinea pigs are discussed.

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Cytokine and chemokine expression in cigarette smoke-induced lung injury in guinea pigs

Cited by 59 publications

References 36 publications

Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells

Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells

Statins inhibit matrix metalloproteinase release from human lung fibroblasts

Using guinea pigs in studies relevant to asthma and COPD

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