Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein
<p>Abstract</p> <p>Background</p> <p>Recent studies suggest that HCV infection is associated with progressive declines in pulmonary function in patients with underlying pulmonary diseases such as asthma and chronic obstructive pulmonary disease. Few molecular studies ha...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2005-09-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/6/1/105 |
| _version_ | 1811257937892474880 |
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| author | Chi David S Lee Steven A Prayther Deborah C Fitzgerald S Matthew Moorman Jonathan P Krishnaswamy Guha |
| author_facet | Chi David S Lee Steven A Prayther Deborah C Fitzgerald S Matthew Moorman Jonathan P Krishnaswamy Guha |
| author_sort | Chi David S |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Recent studies suggest that HCV infection is associated with progressive declines in pulmonary function in patients with underlying pulmonary diseases such as asthma and chronic obstructive pulmonary disease. Few molecular studies have addressed the inflammatory aspects of HCV-associated pulmonary disease. Because IL-8 plays a fundamental role in reactive airway diseases, we examined IL-8 signaling in normal human lung fibroblasts (NHLF) in response to the HCV nucleocapsid core protein, a viral antigen shown to modulate intracellular signaling pathways involved in cell proliferation, apoptosis and inflammation.</p> <p>Methods</p> <p>NHLF were treated with HCV core protein and assayed for IL-8 expression, phosphorylation of the p38 MAPK pathway, and for the effect of p38 inhibition.</p> <p>Results</p> <p>Our studies demonstrate that soluble HCV core protein induces significant increases in both IL-8 mRNA and protein expression in a dose- and time-dependent manner. Treatment with HCV core led to phosphorylation of p38 MAPK, and expression of IL-8 was dependent upon p38 activation. Using TNFα as a co-stimulant, we observed additive increases in IL-8 expression. HCV core-mediated expression of IL-8 was inhibited by blocking gC1qR, a known receptor for soluble HCV core linked to MAPK signaling.</p> <p>Conclusion</p> <p>These studies suggest that HCV core protein can lead to enhanced p38- and gC1qR-dependent IL-8 expression. Such a pro-inflammatory role may contribute to the progressive deterioration in pulmonary function recently recognized in individuals chronically infected with HCV.</p> |
| first_indexed | 2024-04-12T18:05:14Z |
| format | Article |
| id | doaj.art-6c62c009be75490d8fd9ba47b5f9133d |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-04-12T18:05:14Z |
| publishDate | 2005-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-6c62c009be75490d8fd9ba47b5f9133d2022-12-22T03:22:00ZengBMCRespiratory Research1465-99212005-09-016110510.1186/1465-9921-6-105Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core proteinChi David SLee Steven APrayther Deborah CFitzgerald S MatthewMoorman Jonathan PKrishnaswamy Guha<p>Abstract</p> <p>Background</p> <p>Recent studies suggest that HCV infection is associated with progressive declines in pulmonary function in patients with underlying pulmonary diseases such as asthma and chronic obstructive pulmonary disease. Few molecular studies have addressed the inflammatory aspects of HCV-associated pulmonary disease. Because IL-8 plays a fundamental role in reactive airway diseases, we examined IL-8 signaling in normal human lung fibroblasts (NHLF) in response to the HCV nucleocapsid core protein, a viral antigen shown to modulate intracellular signaling pathways involved in cell proliferation, apoptosis and inflammation.</p> <p>Methods</p> <p>NHLF were treated with HCV core protein and assayed for IL-8 expression, phosphorylation of the p38 MAPK pathway, and for the effect of p38 inhibition.</p> <p>Results</p> <p>Our studies demonstrate that soluble HCV core protein induces significant increases in both IL-8 mRNA and protein expression in a dose- and time-dependent manner. Treatment with HCV core led to phosphorylation of p38 MAPK, and expression of IL-8 was dependent upon p38 activation. Using TNFα as a co-stimulant, we observed additive increases in IL-8 expression. HCV core-mediated expression of IL-8 was inhibited by blocking gC1qR, a known receptor for soluble HCV core linked to MAPK signaling.</p> <p>Conclusion</p> <p>These studies suggest that HCV core protein can lead to enhanced p38- and gC1qR-dependent IL-8 expression. Such a pro-inflammatory role may contribute to the progressive deterioration in pulmonary function recently recognized in individuals chronically infected with HCV.</p>http://respiratory-research.com/content/6/1/105 |
| spellingShingle | Chi David S Lee Steven A Prayther Deborah C Fitzgerald S Matthew Moorman Jonathan P Krishnaswamy Guha Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein Respiratory Research |
| title | Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein |
| title_full | Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein |
| title_fullStr | Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein |
| title_full_unstemmed | Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein |
| title_short | Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein |
| title_sort | induction of p38 and gc1qr dependent il 8 expression in pulmonary fibroblasts by soluble hepatitis c core protein |
| url | http://respiratory-research.com/content/6/1/105 |
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