CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor
Background/Aims: The chemokine CXCL1 has been reported to be expressed in lung airway epithelium and non-small cell lung cancer biopsy specimens. In this study, we investigated the effects of TNF-α, an abundant cytokine detected in inflammation and various cancers, on CXCL1 release by human A549 lun...
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Cell Physiol Biochem Press GmbH & Co KG
2014-10-01
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doaj-0ce425d0841445c38db0d9e86fc29eba2020-11-25T01:37:49ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782014-10-013441373138410.1159/000366344366344CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis FactorJiunn-Min ShiehYih-Jeng TsaiChih-Jen TsouWen-Bin WuBackground/Aims: The chemokine CXCL1 has been reported to be expressed in lung airway epithelium and non-small cell lung cancer biopsy specimens. In this study, we investigated the effects of TNF-α, an abundant cytokine detected in inflammation and various cancers, on CXCL1 release by human A549 lung carcinoma epithelial cells. Methods: CXCL1 expression was determined by ELISA and RT-PCR. TNF-α signaling was examined by western blotting. Monocyte migration was assayed by a Transwell migration system. Results: TNF-α stimulated CXCL1 release and mRNA expression, and this release was inhibited by inhibitors of JNK, p38 MAPK, PI-3K/Akt and AP-1 transcription factor. TNF-α treatment was followed by JNK, p38 MAPK and PI3K/Akt activation. However, only the JNK inhibitor could reduce the CXCL1 mRNA level, suggesting that JNK is required mainly for CXCL1 mRNA synthesis, whereas p38 MAPK and PI-3K/Akt might be responsible for CXCL1 secretion. Dexamethasone (dex) and TGF-β reduced CXCL1 secretion, with dex upregulating the expression of MAP kinase phosphatase-1 and TGF-β causing smad2/3 activation and nuclear translocation. A functional analysis showed that the released CXCL1 enhanced monocyte migration and could be abolished by a CXCL1 neutralizing antibody and CXCR antagonist. Conclusion: We demonstrate that TNF-α induces CXCL1 expression through the JNK, p38 MAPK and PI-3K/Akt signaling pathways in human pulmonary epithelial cells.http://www.karger.com/Article/FullText/366344ChemokineCXCL1JNKGro alphaTNFSignalingReleaseSecretion |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiunn-Min Shieh Yih-Jeng Tsai Chih-Jen Tsou Wen-Bin Wu |
spellingShingle |
Jiunn-Min Shieh Yih-Jeng Tsai Chih-Jen Tsou Wen-Bin Wu CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor Cellular Physiology and Biochemistry Chemokine CXCL1 JNK Gro alpha TNF Signaling Release Secretion |
author_facet |
Jiunn-Min Shieh Yih-Jeng Tsai Chih-Jen Tsou Wen-Bin Wu |
author_sort |
Jiunn-Min Shieh |
title |
CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor |
title_short |
CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor |
title_full |
CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor |
title_fullStr |
CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor |
title_full_unstemmed |
CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor |
title_sort |
cxcl1 regulation in human pulmonary epithelial cells by tumor necrosis factor |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2014-10-01 |
description |
Background/Aims: The chemokine CXCL1 has been reported to be expressed in lung airway epithelium and non-small cell lung cancer biopsy specimens. In this study, we investigated the effects of TNF-α, an abundant cytokine detected in inflammation and various cancers, on CXCL1 release by human A549 lung carcinoma epithelial cells. Methods: CXCL1 expression was determined by ELISA and RT-PCR. TNF-α signaling was examined by western blotting. Monocyte migration was assayed by a Transwell migration system. Results: TNF-α stimulated CXCL1 release and mRNA expression, and this release was inhibited by inhibitors of JNK, p38 MAPK, PI-3K/Akt and AP-1 transcription factor. TNF-α treatment was followed by JNK, p38 MAPK and PI3K/Akt activation. However, only the JNK inhibitor could reduce the CXCL1 mRNA level, suggesting that JNK is required mainly for CXCL1 mRNA synthesis, whereas p38 MAPK and PI-3K/Akt might be responsible for CXCL1 secretion. Dexamethasone (dex) and TGF-β reduced CXCL1 secretion, with dex upregulating the expression of MAP kinase phosphatase-1 and TGF-β causing smad2/3 activation and nuclear translocation. A functional analysis showed that the released CXCL1 enhanced monocyte migration and could be abolished by a CXCL1 neutralizing antibody and CXCR antagonist. Conclusion: We demonstrate that TNF-α induces CXCL1 expression through the JNK, p38 MAPK and PI-3K/Akt signaling pathways in human pulmonary epithelial cells. |
topic |
Chemokine CXCL1 JNK Gro alpha TNF Signaling Release Secretion |
url |
http://www.karger.com/Article/FullText/366344 |
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