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IL-27 alleviates the bleomycin-induced pulmonary fibrosis by regulating the Th17 cell differentiation.

Dong Z, Lu X, Yang Y, Zhang T, Li Y, Chai Y, Lei W, Li C, Ai L, Tai W - BMC Pulm Med (2015)

Bottom Line: IL-27 inhibited the development of CD4(+) IL-17(+), CD4(+) IL-4(+) T, and CD4(+) Foxp3(+) cells and the secretion of IL-17, IL-4, IL-6, and TGF-ß.IL-27 induced the production of CD4(+) IL-10(+) and CD4(+) INF-γ(+) T cells.IL-27 decreased the levels of phosphorylated STAT1, STAT3, STAT5, Smad1, and Smad3 but increased the level of SOCS3.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. dongkm@hotmail.com.

ABSTRACT

Background: Interleukin-27 (IL-27) is a multifunctional cytokine with both pro-inflammatory and immunoregulatory functions. At present, the role of IL-27 in pulmonary fibrosis remains unknown.

Methods: In this study, we observed the expression of IL-27/IL-27R in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We verified the role of IL-27 using hematoxylin and eosin as well as Masson's staining methods and measuring the content of hydroxyproline as well as collagen I and III. We assessed the differentiation of T lymphocytes in the spleen and measured the concentration of cytokines in bronchoalveolar lavage fluid (BALF) and the expression level of relevant proteins in the JAK/STAT and TGF-ß/Smad signaling pathways in lung tissue.

Results: Increased IL-27 expression in BLM-induced pulmonary fibrosis was noted. IL-27 treatment may alleviate pulmonary fibrosis and increase the survival of mice. IL-27 inhibited the development of CD4(+) IL-17(+), CD4(+) IL-4(+) T, and CD4(+) Foxp3(+) cells and the secretion of IL-17, IL-4, IL-6, and TGF-ß. IL-27 induced the production of CD4(+) IL-10(+) and CD4(+) INF-γ(+) T cells. IL-27 decreased the levels of phosphorylated STAT1, STAT3, STAT5, Smad1, and Smad3 but increased the level of SOCS3.

Conclusions: This study demonstrates that IL-27 potentially attenuates BLM-induced pulmonary fibrosis by regulating Th17 differentiation and cytokine secretion.

No MeSH data available.


Related in: MedlinePlus

IL-27/IL-27R expression increases in bleomycin-induced pulmonary fibrosis.A. Real-time PCR for IL-27 and IL-27R, at days 3, 7, 14, and 28 in the BLM and control groups. The expression of the CT values for real-time PCR were normalized by 2-∆∆ct. B. IL-27 and IL-27R mRNA expression in the different groups. C, D. Western blot analysis; band intensities were measured using Image J. For each group, n = 3. Data are expressed as the mean ± SEM. *p < 0.05, **p < 0.01.
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Fig1: IL-27/IL-27R expression increases in bleomycin-induced pulmonary fibrosis.A. Real-time PCR for IL-27 and IL-27R, at days 3, 7, 14, and 28 in the BLM and control groups. The expression of the CT values for real-time PCR were normalized by 2-∆∆ct. B. IL-27 and IL-27R mRNA expression in the different groups. C, D. Western blot analysis; band intensities were measured using Image J. For each group, n = 3. Data are expressed as the mean ± SEM. *p < 0.05, **p < 0.01.

Mentions: To explore the role of IL-27 in the pathogenesis of pulmonary fibrosis, we assessed IL-27/IL-27R mRNA expression in BIPF using quantitative RT-PCR. IL-27/IL-27R expression was the highest on day 7 of BIPF(1A, B). We then treated these mice with either IL-27 or an IL-27 antibody and observed the level of IL-27/IL-27R 7 and 28 days later (Figure 1B, C, D). Increased IL-27 was noted in the BLM + IL-27 group compared with the other groups. The level of IL-27 at 28 days was increased compared with the levels observed at 7 days for all groups except the control group. These results indicate that IL-27 may be involved in the formation of BIPF.Figure 1


IL-27 alleviates the bleomycin-induced pulmonary fibrosis by regulating the Th17 cell differentiation.

Dong Z, Lu X, Yang Y, Zhang T, Li Y, Chai Y, Lei W, Li C, Ai L, Tai W - BMC Pulm Med (2015)

IL-27/IL-27R expression increases in bleomycin-induced pulmonary fibrosis.A. Real-time PCR for IL-27 and IL-27R, at days 3, 7, 14, and 28 in the BLM and control groups. The expression of the CT values for real-time PCR were normalized by 2-∆∆ct. B. IL-27 and IL-27R mRNA expression in the different groups. C, D. Western blot analysis; band intensities were measured using Image J. For each group, n = 3. Data are expressed as the mean ± SEM. *p < 0.05, **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4340860&req=5

Fig1: IL-27/IL-27R expression increases in bleomycin-induced pulmonary fibrosis.A. Real-time PCR for IL-27 and IL-27R, at days 3, 7, 14, and 28 in the BLM and control groups. The expression of the CT values for real-time PCR were normalized by 2-∆∆ct. B. IL-27 and IL-27R mRNA expression in the different groups. C, D. Western blot analysis; band intensities were measured using Image J. For each group, n = 3. Data are expressed as the mean ± SEM. *p < 0.05, **p < 0.01.
Mentions: To explore the role of IL-27 in the pathogenesis of pulmonary fibrosis, we assessed IL-27/IL-27R mRNA expression in BIPF using quantitative RT-PCR. IL-27/IL-27R expression was the highest on day 7 of BIPF(1A, B). We then treated these mice with either IL-27 or an IL-27 antibody and observed the level of IL-27/IL-27R 7 and 28 days later (Figure 1B, C, D). Increased IL-27 was noted in the BLM + IL-27 group compared with the other groups. The level of IL-27 at 28 days was increased compared with the levels observed at 7 days for all groups except the control group. These results indicate that IL-27 may be involved in the formation of BIPF.Figure 1

Bottom Line: IL-27 inhibited the development of CD4(+) IL-17(+), CD4(+) IL-4(+) T, and CD4(+) Foxp3(+) cells and the secretion of IL-17, IL-4, IL-6, and TGF-ß.IL-27 induced the production of CD4(+) IL-10(+) and CD4(+) INF-γ(+) T cells.IL-27 decreased the levels of phosphorylated STAT1, STAT3, STAT5, Smad1, and Smad3 but increased the level of SOCS3.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. dongkm@hotmail.com.

ABSTRACT

Background: Interleukin-27 (IL-27) is a multifunctional cytokine with both pro-inflammatory and immunoregulatory functions. At present, the role of IL-27 in pulmonary fibrosis remains unknown.

Methods: In this study, we observed the expression of IL-27/IL-27R in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We verified the role of IL-27 using hematoxylin and eosin as well as Masson's staining methods and measuring the content of hydroxyproline as well as collagen I and III. We assessed the differentiation of T lymphocytes in the spleen and measured the concentration of cytokines in bronchoalveolar lavage fluid (BALF) and the expression level of relevant proteins in the JAK/STAT and TGF-ß/Smad signaling pathways in lung tissue.

Results: Increased IL-27 expression in BLM-induced pulmonary fibrosis was noted. IL-27 treatment may alleviate pulmonary fibrosis and increase the survival of mice. IL-27 inhibited the development of CD4(+) IL-17(+), CD4(+) IL-4(+) T, and CD4(+) Foxp3(+) cells and the secretion of IL-17, IL-4, IL-6, and TGF-ß. IL-27 induced the production of CD4(+) IL-10(+) and CD4(+) INF-γ(+) T cells. IL-27 decreased the levels of phosphorylated STAT1, STAT3, STAT5, Smad1, and Smad3 but increased the level of SOCS3.

Conclusions: This study demonstrates that IL-27 potentially attenuates BLM-induced pulmonary fibrosis by regulating Th17 differentiation and cytokine secretion.

No MeSH data available.


Related in: MedlinePlus