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Pirfenidone exerts a suppressive effect on CCL18 expression in U937-derived macrophages partly by inhibiting STAT6 phosphorylation.
- Source :
-
Immunopharmacology & Immunotoxicology . Dec2016, Vol. 38 Issue 6, p464-471. 8p. - Publication Year :
- 2016
-
Abstract
- Context:CC chemokine ligand 18 (CCL18) is suggested to play a role in the development of pulmonary fibrosis. Macrophages are thought to be the main source of CCL18, and the effect of pirfenidone, an anti-fibrotic agent for idiopathic pulmonary fibrosis, on the expression of CCL18 in macrophages warrants investigation. Objective:The purpose of this study was to investigate the effect of pirfenidone on the expression of CCL18 in macrophages. Materials and methods:U937 cells were differentiated into macrophages by phorbol myristate acetate and then stimulated with recombinant IL-4 to induce the production of CCL18. The cells were treated with pirfenidone, and the mRNA and protein levels for CCL18 were measured by a reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effects of pirfenidone on the IL-4 receptor (IL-4R) expression and STAT6 activation were investigated and on the JAK kinase activity were measured using the Z′-LYTE™ kinase assay. Results:Pirfenidone significantly suppressed the expression of CCL18 when the cells were treated with concentrations of 50–250 μg/mL. Pirfenidone did not affect the expression of the IL-4R components. The selective STAT6 inhibitor AS1517499 suppressed CCL18 expression. Both AS1517499 and pirfenidone suppressed STAT6 phosphorylation (p < .05), although the effect of pirfenidone was less marked than that of AS1517499. The Z′-LYTE™ kinase assay showed a reduction in the activities of JAK1, JAK3 and TYK2 by pirfenidone. Conclusion:Pirfenidone suppresses CCL18 expression in macrophages and this effect is thought to be attributed partly to the inhibition of STAT6 phosphorylation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08923973
- Volume :
- 38
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Immunopharmacology & Immunotoxicology
- Publication Type :
- Academic Journal
- Accession number :
- 119304094
- Full Text :
- https://doi.org/10.1080/08923973.2016.1247852