| Synergy of IL-27 and TNF-α in regulating CXCL10 expression in lung fibroblasts: implications in airway inflammation. | |
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MedLine Citation:
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PMID: 23333920 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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IL-27 is involved in inflammatory reactions. CXCL10 is an important chemokine contributing to airway inflammatory diseases. In this study, we investigated whether IL-27 modulated the synthesis of CXCL10 in primary human lung fibroblasts (HLF). HLF were activated by IL-27 alone, or in combination with other cytokines. CXCL10 synthesis was measured by real-time PCR and ELISA. Examination of transcriptional regulation was performed via transient transfection of promoter constructs, whereas mRNA stability was assessed by actinomycin D chase and real-time PCR. The underlying signaling pathways were studied by Western blot and intracellular staining using flow cytometry. Our results demonstrated that IL-27 induced and synergized with TNF-α to upregulate CXCL10 mRNA and protein levels in a steroid-insensitive manner. This synergistic CXCL10 production was dependent on transcriptional regulation of CXCL10 gene promoter activity and the enhanced stability of CXCL10 mRNA by IL-27 and TNF-α, and this synergism was regulated by the activation of p38 MAPK and PI3K-Akt dominantly and in a little part via NF-kB. Interestingly, IL-27 promoted basal and enhanced TNF-α-induced phosphorylation of p38 MAPK and Akt, but not IkBα. Besides, the enhanced CXCL10 mRNA stability occurred via a p38 MAPK-dependent pathway. Finally, clinical analysis showed that IL-27 was detected in BAL of patients with asthma, COPD, and PTB, and the increased IL-27 levels was correlated with the increased CXCL10 levels in patients with COPD and PTB. Our findings suggest that IL-27 has the potential to amplify airway inflammation via the induction of CXCL10 from HLF in combination with TNF-α. |
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Authors:
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Shanshan Dong; Xuemei Zhang; Yujuan He; Fang Xu; Dairong Li; Wenchun Xu; Hong Wang; Yibing Yin; Ju Cao |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-18 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: - ISSN: 1535-4989 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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