| Title |
Clarithromycin attenuates IL-13–induced periostin production in human lung fibroblasts
|
|---|---|
| Published in |
Respiratory Research, February 2017
|
| DOI | 10.1186/s12931-017-0519-8 |
| Pubmed ID | |
| Authors |
Kosaku Komiya, Shoichiro Ohta, Kazuhiko Arima, Masahiro Ogawa, Shoichi Suzuki, Yasutaka Mitamura, Satoshi Nunomura, Yasuhiro Nanri, Tomohito Yoshihara, Atsushi Kawaguchi, Jun-ichi Kadota, Bruce K. Rubin, Kenji Izuhara |
| Abstract |
Periostin is a biomarker indicating the presence of type 2 inflammation and submucosal fibrosis; serum periostin levels have been associated with asthma severity. Macrolides have immunomodulatory effects and are considered a potential therapy for patients with severe asthma. Therefore, we investigated whether macrolides can also modulate pulmonary periostin production. Using quantitative PCR and ELISA, we measured periostin production in human lung fibroblasts stimulated by interleukin-13 (IL-13) in the presence of two 14-member-ring macrolides-clarithromycin or erythromycin-or a 16-member-ring macrolide, josamycin. Phosphorylation of signal transducers and activators of transcription 6 (STAT6), downstream of IL-13 signaling, was evaluated by Western blotting. Changes in global gene expression profile induced by IL-13 and/or clarithromycin were assessed by DNA microarray analysis. Clarithromycin and erythromycin, but not josamycin, inhibited IL-13-stimulated periostin production. The inhibitory effects of clarithromycin were stronger than those of erythromycin. Clarithromycin significantly attenuated STAT6 phosphorylation induced by IL-13. Global gene expression analyses demonstrated that IL-13 increased mRNA expression of 454 genes more than 4-fold, while decreasing its expression in 390 of these genes (85.9%), mainly "extracellular," "plasma membrane," or "defense response" genes. On the other hand, clarithromycin suppressed 9.8% of the genes in the absence of IL-13. Clarithromycin primarily attenuated the gene expression of extracellular matrix protein, including periostin, especially after IL-13. Clarithromycin suppressed IL-13-induced periostin production in human lung fibroblasts, in part by inhibiting STAT6 phosphorylation. This suggests a novel mechanism of the immunomodulatory effect of clarithromycin in asthmatic airway inflammation and fibrosis. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 19% |
| Student > Ph. D. Student | 3 | 12% |
| Professor | 2 | 8% |
| Lecturer > Senior Lecturer | 2 | 8% |
| Other | 2 | 8% |
| Other | 5 | 19% |
| Unknown | 7 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 42% |
| Agricultural and Biological Sciences | 4 | 15% |
| Linguistics | 1 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Biochemistry, Genetics and Molecular Biology | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 7 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 March 2017.
All research outputs
#15,173,117
of 25,382,440 outputs
Outputs from Respiratory Research
#1,601
of 3,062 outputs
Outputs of similar age
#173,695
of 323,273 outputs
Outputs of similar age from Respiratory Research
#24
of 47 outputs
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