p38 MAP kinase regulates TNFα‐, IL‐1α‐ and PAF‐induced RANTES and GM‐CSF production by human bronchial epithelial cells

Hashimoto, Shigeo; Matsumoto, Ken; Gon, Yasuhiro; Maruoka, Shuichiro; Kujime, Kosei; Hayashi, S.; Takeshita, Ikuko; Horie, Takashi

doi:10.1046/j.1365-2222.2000.00641.x

Cited by 70 publications

(46 citation statements)

References 34 publications

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“…p38 MAPK inhibition affected the PDT-induced expression of immune and inflammatory response mediators, such as COX-2 (PTGS2), GM-CSF (granulocyte macrophage colony-stimulating factor; CSF2), interleukin 8 (IL8) and the Toll-like receptor 2, as also reported in previous studies (Hashimoto et al, 2000;Hoffmann et al, 2002;Imasato et al, 2002). Notably, the expression of a number of stress-responsive genes encoding antioxidant and Phase II drug-metabolizing enzymes (Table 2), with an established role in cellular protection following oxidative damage caused by ROS or electrophiles (Lee and Johnson, 2004) was found to be significantly attenuated by PD169316.…”

Section: Global Distribution Of Hypericin-pdt Differentially Expressesupporting

confidence: 76%

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Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

et al. 2007

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Photodynamic therapy (PDT) is an anticancer approach utilizing a light-absorbing molecule and visible light irradiation to generate, in the presence of O 2 , cytotoxic reactive oxygen species, which cause tumor ablation. Given that the photosensitizer hypericin is under consideration for PDT treatment of bladder cancer we used oligonucleotide microarrays in the T24 bladder cancer cell line to identify differentially expressed genes with therapeutic potential. This study reveals that the expression of several genes involved in various metabolic processes, stress-induced cell death, autophagy, proliferation, inflammation and carcinogenesis is strongly affected by PDT and pinpoints the coordinated induction of a cluster of genes involved in the unfolded protein response pathway after endoplasmic reticulum stress and in antioxidant response. Analysis of PDT-treated cells after p38 MAPK inhibition or silencing unraveled that the induction of an important subset of differentially expressed genes regulating growth and invasion, as well as adaptive mechanisms against oxidative stress, is governed by this stress-activated kinase. Moreover, p38 MAPK inhibition blocked autonomous regrowth and migration of cancer cells escaping PDT-induced cell death. This analysis identifies new molecular effectors of the cancer cell response to PDT opening attractive avenues to improve the therapeutic efficacy of hypericin-based PDT of bladder cancer.

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Section: Global Distribution Of Hypericin-pdt Differentially Expressesupporting

confidence: 76%

“…Thus, the p38 MAPK pathway in PDT-treated T24 cells could rapidly stabilize and increase translation of AREs-containing labile mRNAs, for example, for MMP-13, COX-2 and GM-CSF, involved in tumor promotion (Hashimoto et al, 2000;Hoffmann et al, 2002;Dean et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

et al. 2007

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“…Although airway epithelial cells are well recognized as potent sources of cytokines such as IL-6, IL-8 (5, 19), IL-16 (1), GM-CSF (5,19,26), TGF-␤ (12, 18), endothelin-1 (23), RANTES (8), and eotaxin (16), little is known regarding the effects of culture technique and cellular differentiation on the capacity of the airway epithelium to produce these factors under baseline conditions, or in response to cytokines present in the asthmatic airway. Whereas previous reports have demonstrated that NHBE cells produce GM-CSF and TGF-␤ 2 under baseline conditions, and increase production of both under the influence of Th2 cytokines (20,31), these reports have been limited to submerged monolayer cultures.…”

Section: Discussionmentioning

confidence: 99%

Differentiation-dependent responsiveness of bronchial epithelial cells to IL-4/13 stimulation

Kikuchi¹,

Shively²,

Foley³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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/ajplung.00365.2003.-The Th2 cytokines interleukin (IL)-4 and IL-13 are thought to play critical roles in the airway inflammation and hyperresposiveness that characterize asthma. Recent evidence indicates that IL-13 can mediate these effects by acting directly on airway epithelial cells. Here we evaluated early [signal transducer and activator of transcription (STAT)6 phosphorylation] and delayed [granulocyte/macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-␤ 2 (TGF-␤2) secretion] responses of airway epithelial cells to IL-4 and IL-13 stimulation and the dependence of these responses on the culture technique employed. As expected, normal human bronchial epithelial cells grown on microporous inserts at an air-liquid interface (ALI) expressed a well-differentiated mucociliary phenotype; in contrast, cells grown on plastic in submerged cultures were poorly differentiated. When stimulated with IL-4 or IL-13, the magnitude and duration of STAT6 phosphorylation under the differing culture conditions were statistically indistinguishable. In contrast, cytokine secretion responses to IL-4 and IL-13 were highly dependent on the culture technique; cells cultured on plastic exhibited significant concentration-dependent increases in GM-CSF and TGF-␤ 2 secretion, whereas cells grown at ALI showed no statistically significant response. These results demonstrate that the coupling between early signal transduction responses to IL-4 and IL-13 and downstream functions such as cytokine secretion may be critically dependent on the cell culture technique employed and the resulting differentiation status of bronchial epithelial cells.bronchial epithelial cells; cell differentiation; interleukin-4/13; granulocyte/macrophage colony-stimulating factor; transforming growth factor-␤ THE TH2 CYTOKINES interleukin (IL)-4 and IL-13 have been shown to play critical roles in allergic inflammation and the development of airway hyperresponsiveness (AHR; see Ref. 32). Although both cytokines play key roles in T-cell phenotypic commitment and IgE production (32, 34), recent evidence demonstrates that IL-13 can mediate the development of AHR by direct action on airway epithelial cells (13). These results underscore the need to understand the gene and protein responses evoked in the airway epithelium by IL-4 and, especially, IL-13.In vivo, the airway epithelium is composed of a mixed population of ciliated, nonciliated, and mucous-secreting cells (10). Studies using bronchial epithelial cell cultures differentiated to induce a mucociliary phenotype have shown that IL-4 and IL-13 stimulation modulate basic cell functions such as proliferation (3), ciliary beating, and mucous production (2, 14, 25). In contrast, our growing understanding of the ability of Th2 cytokines to stimulate gene expression (15) and production of soluble factors (4,17,20,24,31) is derived primarily from study of submerged cultures of airway epithelial cells grown on plastic, conditions that result in a poorly differentiated, proliferating cell popula...

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“…For example, the current authors have shown previously that human bronchial epithelial cells respond to interleukin (IL)-4 and IL-13 with tyrosine phosphorylation of STAT (signal transducer and activator of transcription)6 mediated by members of the JAK (Janus kinase) family [20]. Bronchial epithelial cells also respond to environmental stress and endogenous cytokines, such as tumour necrosis factor (TNF)-a and IL-1b through activation of p38 MAPK [21] and jun N-terminal kinase (JNK) [22].…”

mentioning

confidence: 91%

Altered protein tyrosine phosphorylation in asthmatic bronchial epithelium

Hamilton

Puddicombe²,

Dearman³

et al. 2005

European Respiratory Journal

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A disease-related, corticosteroid-insensitive increase in the expression of epidermal growth factor (EGF) receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium has been shown previously by the current authors. To determine whether this is associated with enhanced intracellular signalling, the aim of this study was to evaluate epithelial tyrosine phosphorylation.Bronchial biopsies were analysed for the presence of phosphotyrosine by immunohistochemistry. Bronchial epithelial cells were exposed to EGF, hydrogen peroxide or tumour necrosis factor-a in vitro for measurement of tyrosine phosphorylated signalling intermediates and interleukin (IL)-8 release.Phosphotyrosine was increased significantly in the epithelium of severe asthmatics when compared with controls or mild asthmatics; however, in mild asthma, phosphotyrosine levels were significantly decreased when compared with controls. There was no significant difference between phosphotyrosine levels before or after 8 weeks of treatment with budesonide. Stimulation of bronchial epithelial cells resulted in tyrosine phosphorylation of several proteins, including EGFR, Shc and p42/p44 mitogen-activated protein kinase. In the presence of salbutamol, a transient partial suppression of EGFR phosphorylation occurred, whereas dexamethasone was without effect. Neither salbutamol nor dexamethasone inhibited EGFstimulated IL-8 release.These data indicate that regulation of protein tyrosine kinase activity is abnormal in severe asthma. The epidermal growth factor receptor and/or other tyrosine kinase pathways may contribute to persistent, corticosteroid-unresponsive inflammation in severe asthma.

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p38 MAP kinase regulates TNFα‐, IL‐1α‐ and PAF‐induced RANTES and GM‐CSF production by human bronchial epithelial cells

Cited by 70 publications

References 34 publications

Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

Differentiation-dependent responsiveness of bronchial epithelial cells to IL-4/13 stimulation

Altered protein tyrosine phosphorylation in asthmatic bronchial epithelium

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