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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

Exogenous IL-27 treatment can suppress BLM-induced pulmonary fibrosis.A. Hematoxylin and eosin (HE) staining (100x) and Masson’s trichrome staining (100x) depicting the effects of exogenous IL-27 application on lung histological changes at days 7 and 28 in various treated mice. B. The alveolitis and fibrosis scores for the lungs of mice in the different groups at days 7 and 28. Values are means ± SEM (n = 5). C, D, E. Real-time PCR and Western blot analysis for COL1 and COL3, respectively, in the different groups. CT values for the real-time PCR were normalized by 2-∆∆ct. Western band intensities were measured using Image J software. For each group, n = 3. F. The lung hydroxyproline content at days 7 and 28 for mice in the various treatment groups. Hydroxyproline content was measured using an ELISA, n = 5. G. Survival rate of mice with BLM-induced pulmonary fibrosis. The percentage of survival over time is presented, n = 5. Data are expressed as means ± SEM. *p < 0.05, **p < 0.01. A: control, B: BLM group, C: BLM + IL-27 group, D: BLM + IL-27 antibody group.
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Fig2: Exogenous IL-27 treatment can suppress BLM-induced pulmonary fibrosis.A. Hematoxylin and eosin (HE) staining (100x) and Masson’s trichrome staining (100x) depicting the effects of exogenous IL-27 application on lung histological changes at days 7 and 28 in various treated mice. B. The alveolitis and fibrosis scores for the lungs of mice in the different groups at days 7 and 28. Values are means ± SEM (n = 5). C, D, E. Real-time PCR and Western blot analysis for COL1 and COL3, respectively, in the different groups. CT values for the real-time PCR were normalized by 2-∆∆ct. Western band intensities were measured using Image J software. For each group, n = 3. F. The lung hydroxyproline content at days 7 and 28 for mice in the various treatment groups. Hydroxyproline content was measured using an ELISA, n = 5. G. Survival rate of mice with BLM-induced pulmonary fibrosis. The percentage of survival over time is presented, n = 5. Data are expressed as means ± SEM. *p < 0.05, **p < 0.01. A: control, B: BLM group, C: BLM + IL-27 group, D: BLM + IL-27 antibody group.

Mentions: To verify the role of IL-27 in BIPF, the mice were divided into four groups: a control group, BLM group, BLM + IL-27 group, and BLM + IL-27 antibody group. HE staining revealed a disordered lung tissue structure; the pulmonary interalveolar septa were thickened and infiltrated by inflammatory cells, and a large number of alveoli were collapsed. These observations were consolidated in the BLM group and most severe in the BLM + IL-27 antibody group, whereas injected IL-27 alleviated the degree of alveolitis. Based on Masson’s staining, wherein blue stain represents the fibroblasts and collagen matrix, a similar trend was observed (Figure 2A, B).Figure 2


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)

Exogenous IL-27 treatment can suppress BLM-induced pulmonary fibrosis.A. Hematoxylin and eosin (HE) staining (100x) and Masson’s trichrome staining (100x) depicting the effects of exogenous IL-27 application on lung histological changes at days 7 and 28 in various treated mice. B. The alveolitis and fibrosis scores for the lungs of mice in the different groups at days 7 and 28. Values are means ± SEM (n = 5). C, D, E. Real-time PCR and Western blot analysis for COL1 and COL3, respectively, in the different groups. CT values for the real-time PCR were normalized by 2-∆∆ct. Western band intensities were measured using Image J software. For each group, n = 3. F. The lung hydroxyproline content at days 7 and 28 for mice in the various treatment groups. Hydroxyproline content was measured using an ELISA, n = 5. G. Survival rate of mice with BLM-induced pulmonary fibrosis. The percentage of survival over time is presented, n = 5. Data are expressed as means ± SEM. *p < 0.05, **p < 0.01. A: control, B: BLM group, C: BLM + IL-27 group, D: BLM + IL-27 antibody group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Exogenous IL-27 treatment can suppress BLM-induced pulmonary fibrosis.A. Hematoxylin and eosin (HE) staining (100x) and Masson’s trichrome staining (100x) depicting the effects of exogenous IL-27 application on lung histological changes at days 7 and 28 in various treated mice. B. The alveolitis and fibrosis scores for the lungs of mice in the different groups at days 7 and 28. Values are means ± SEM (n = 5). C, D, E. Real-time PCR and Western blot analysis for COL1 and COL3, respectively, in the different groups. CT values for the real-time PCR were normalized by 2-∆∆ct. Western band intensities were measured using Image J software. For each group, n = 3. F. The lung hydroxyproline content at days 7 and 28 for mice in the various treatment groups. Hydroxyproline content was measured using an ELISA, n = 5. G. Survival rate of mice with BLM-induced pulmonary fibrosis. The percentage of survival over time is presented, n = 5. Data are expressed as means ± SEM. *p < 0.05, **p < 0.01. A: control, B: BLM group, C: BLM + IL-27 group, D: BLM + IL-27 antibody group.
Mentions: To verify the role of IL-27 in BIPF, the mice were divided into four groups: a control group, BLM group, BLM + IL-27 group, and BLM + IL-27 antibody group. HE staining revealed a disordered lung tissue structure; the pulmonary interalveolar septa were thickened and infiltrated by inflammatory cells, and a large number of alveoli were collapsed. These observations were consolidated in the BLM group and most severe in the BLM + IL-27 antibody group, whereas injected IL-27 alleviated the degree of alveolitis. Based on Masson’s staining, wherein blue stain represents the fibroblasts and collagen matrix, a similar trend was observed (Figure 2A, B).Figure 2

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