Involvement of p42/p44 MAPK, p38 MAPK, JNK, and NF-κB in IL-1β-induced VCAM-1 expression in human tracheal smooth muscle cells

Wang, Chien-Chun; Lin, Wei‐Ning; Lee, Chiang‐Wen; Lin, Chih-Chung; Luo, Shue‐Fen; Wang, Jong‐Shyan; Yang, Che‐Hua

doi:10.1152/ajplung.00224.2004

Cited by 71 publications

(79 citation statements)

References 54 publications

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“…In the present study, we showed that ERK, which is also a downstream signaling molecule of the VEGF pathway, is involved, at least in part, in this process. It has also been shown that the ERK signal transduction pathway is important in VCAM-1 expression (62). In the present study, our data show that hypoxiainduced VCAM-1 expression is diminished in IL-4 KO lungs, suggesting that IL-4 plays an important role in hypoxia-induced VCAM-1 expression and the subsequent inflammatory responses.…”

Section: Discussionsupporting

confidence: 74%

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

Yamaji-Kegan

Angelini

et al. 2009

The Journal of Immunology

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IL-4-mediated proangiogenic and proinflammatory vascular responses have been implicated in the pathogenesis of chronic lung diseases such as asthma. Although it is well known that hypoxia induces pulmonary angiogenesis and vascular alterations, the underlying mechanism of IL-4 on the pulmonary vasculature under hypoxic conditions remains unknown. In this context, we designed the present study to determine the functional importance of IL-4 for pulmonary angiogenesis under hypoxic conditions using IL-4 knockout (KO) animals. Our results show that hypoxia significantly increased IL-4Rα expression in wild-type (WT) control lungs. Even though hypoxia significantly up-regulated vascular endothelial growth factor (VEGF) receptor expression in the lungs of both genotypes, hypoxia-induced VEGF, VCAM-1, HIF-1α, and ERK phosphorylation were significantly diminished in IL-4 KO lungs as compared with WT control lungs. In addition, hypoxia-induced pulmonary angiogenesis and proliferating activities in the airway and pulmonary artery were significantly suppressed in IL-4 KO lungs as compared with WT control lungs. We also isolated primary lung fibroblasts from these genotypes and stimulated these cells with hypoxia. Hypoxia-induced VEGF production was significantly suppressed in lung fibroblasts from IL-4 KO mice. These in vitro results are in accordance with the in vivo data. Furthermore, we observed a significant increase of hypoxia-induced pulmonary angiogenesis in STAT6 KO mice similar to that in WT controls. In conclusion, IL-4 has proangiogenic properties in the lung under hypoxic conditions via the VEGF pathway, and this is independent of the STAT6 pathway.

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Section: Discussionsupporting

confidence: 74%

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

Yamaji-Kegan

Angelini

et al. 2009

The Journal of Immunology

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“…The GRO-␣ promoter region contains NF-B DNA binding sites (14), and NF-B activation represents an important pathway mediating GRO-␣ secretion in several cell types, including ASMC. Both IL-1␤ and TNF-␣ stimulate NF-B activation in ASMC (15,16), and TNF-␣-induced expression of the chemokines, IL-8 and eotaxin, has been shown to be NF-B dependent (17,18). We have shown that GRO-␣ expression is dependent on the activation of NF-B because an inhibitor of the I B kinase complex that promotes the degradation of I B proteins and activates NF-B inhibited IL-1␤-and TNF-␣-induced GRO-␣ expression (5).…”

Section: Discussionmentioning

confidence: 98%

Corticosteroid Inhibition of Growth-Related Oncogene Protein-α via Mitogen-Activated Kinase Phosphatase-1 in Airway Smooth Muscle Cells

Issa

Xie

Khorasani

et al. 2007

The Journal of Immunology

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Expression of the inflammatory chemokine, growth-related oncogene protein-α (GRO-α), from airway smooth muscle cells (ASMC) is regulated by pathways involving NF-κB and MAPK activation. We determined the effects of dexamethasone on GRO-α induced by IL-1β or TNF-α with respect to the role of MAPK pathways and of MAPK phosphatase-1 (MKP-1). Human ASMC were studied in primary culture at confluence. Dexamethasone (10−8–10−5 M) partially inhibited GRO-α expression and release induced by IL-1β and TNF-α; this was associated with an inhibition of JNK, but not of p38 or ERK phosphorylation. Together with IL-1β or TNF-α, dexamethasone rapidly induced mRNA and protein expression of MKP-1, which dephosphorylates MAPKs. Using MKP-1 small interfering RNA (siRNA) to block the expression of IL-1β- and dexamethasone-induced MKP-1 by 50%, JNK phosphorylation was doubled. The inhibitory effect of dexamethasone on GRO-α release was partially reversed in ASMC treated with MKP-1 siRNA compared with those treated with scrambled siRNA. In contrast, overexpression of MKP-1 led to a reduction in IL-1β-induced release of GRO-α, but the inhibitory effects of dexamethasone were preserved. Nuclear translocation of the glucocorticoid receptor was increased in ASMC exposed to dexamethasone and IL-1β. Using chromatin immunoprecipitation assay, glucocorticoid receptor binding to the MKP-1 promoter was increased by IL-1β and dexamethasone compared with either alone. Glucocorticoids and IL-1β or TNF-α modulate GRO-α release partly through the inhibition of JNK pathway, resulting from an up-regulation of MKP-1 expression.

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“…After washing twice with ice-cold PBS, cells were fixed, permeabilized, and stained using an anti-p65 or anti-Nrf2 Ab as previously described. 18 The images were observed using a fluorescence microscope (Zeiss, Axiovert 200M).…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

Overexpression of HO-1 Protects against TNF-α-Mediated Airway Inflammation by Down-Regulation of TNFR1-Dependent Oxidative Stress

Lee

Luo

Lee

et al. 2009

The American Journal of Pathology

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160

151

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Oxidative stresses are believed to play an important role in the induction of both cell adhesion molecules and pro-inflammatory cytokines, a key event in a variety of inflammatory processes. The enzyme heme oxygenase-1 (HO-1) functions as an antioxidant and serves to protect against tissue injury. In this study, we report that HO-1 was induced in cultured human tracheal smooth muscle cells after either treatment with a potent inducer of HO-1 activity, cobalt protoporphyrin IX, or infection with a recombinant adenovirus that carries the human HO-1 gene. Overexpression of HO-1 protected against tumor necrosis factor (TNF)-␣-mediated airway inflammation via the down-regulation of oxidative stress, adhesion molecules, and interleukin-6 in both cultured human tracheal smooth muscle cells and the airways of mice. In addition, HO-1 overexpression inhibited TNF-␣-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, adherence of THP-1 cells, generation of interleukin-6, p47 phox translocation, and nuclear factor-B activation. HO-1 overexpression also attenuated TNF-␣-induced oxidative stress, which was abrogated in the presence of both the HO-1 inhibitor, zinc protoporphyrin IX, as well as a carbon monoxide scavenger. In addition, HO-1 overexpression reduced the formation of a TNFR1/c-Src/p47 phox complex. These results suggest that HO-1 functions as a suppressor of TNF-␣ signaling, not only by inhibiting the expression of adhesion molecules and generation of interleukin-6, but also by diminishing intracellular reactive oxygen species production and nuclear factor-B activation in both cultured human tracheal smooth muscle cells and the airways of mice.

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Involvement of p42/p44 MAPK, p38 MAPK, JNK, and NF-κB in IL-1β-induced VCAM-1 expression in human tracheal smooth muscle cells

Cited by 71 publications

References 54 publications

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

Corticosteroid Inhibition of Growth-Related Oncogene Protein-α via Mitogen-Activated Kinase Phosphatase-1 in Airway Smooth Muscle Cells

Overexpression of HO-1 Protects against TNF-α-Mediated Airway Inflammation by Down-Regulation of TNFR1-Dependent Oxidative Stress

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