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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

The effect of IL-27 treatment on T lymphocyte differentiation in the spleen after 28 days.A. Representative figures from flow cytometry analyses; CD4+ IL-4+, CD4+ IL-10+, CD4+ IL-17+, CD4+ Foxp3+ and CD4+ IFN-γ+ cells from the spleen were analyzed on day 28. B. Analyzed data. Values are expressed as means ± SEM (n = 3). *p < 0.05, **p < 0.01.
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Fig3: The effect of IL-27 treatment on T lymphocyte differentiation in the spleen after 28 days.A. Representative figures from flow cytometry analyses; CD4+ IL-4+, CD4+ IL-10+, CD4+ IL-17+, CD4+ Foxp3+ and CD4+ IFN-γ+ cells from the spleen were analyzed on day 28. B. Analyzed data. Values are expressed as means ± SEM (n = 3). *p < 0.05, **p < 0.01.

Mentions: To explore the mechanisms by which IL-27 inhibits BIPF, we evaluated T lymphocyte differentiation in spleen tissues at day 28. Using intracellular fluorescence staining as assessed by flow cytometry, we measured the CD4+ cells also expressing Foxp3, IL-10, IL-17, IFN-γ, and IL-4. Compared with the control group, the BLM and BLM + IL-27 antibody groups exhibited increased numbers of IL-4-producing CD4+ cells, IL-10-producing CD4+ cells and IL-17-producing CD4+ cells as well as a reduced number of IFN-γ − producing CD4+ cells and Foxp3-producing CD4+ cells. However, after the IL-27 treatment, these expression patterns were reversed with the exception of the IL-10-producing CD4+ cells (Figure 3A, B). The above findings suggest that IL-27 inhibits pulmonary fibrosis by regulating T lymphocyte differentiation in the spleen.Figure 3


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)

The effect of IL-27 treatment on T lymphocyte differentiation in the spleen after 28 days.A. Representative figures from flow cytometry analyses; CD4+ IL-4+, CD4+ IL-10+, CD4+ IL-17+, CD4+ Foxp3+ and CD4+ IFN-γ+ cells from the spleen were analyzed on day 28. B. Analyzed data. Values are expressed as means ± SEM (n = 3). *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

Fig3: The effect of IL-27 treatment on T lymphocyte differentiation in the spleen after 28 days.A. Representative figures from flow cytometry analyses; CD4+ IL-4+, CD4+ IL-10+, CD4+ IL-17+, CD4+ Foxp3+ and CD4+ IFN-γ+ cells from the spleen were analyzed on day 28. B. Analyzed data. Values are expressed as means ± SEM (n = 3). *p < 0.05, **p < 0.01.
Mentions: To explore the mechanisms by which IL-27 inhibits BIPF, we evaluated T lymphocyte differentiation in spleen tissues at day 28. Using intracellular fluorescence staining as assessed by flow cytometry, we measured the CD4+ cells also expressing Foxp3, IL-10, IL-17, IFN-γ, and IL-4. Compared with the control group, the BLM and BLM + IL-27 antibody groups exhibited increased numbers of IL-4-producing CD4+ cells, IL-10-producing CD4+ cells and IL-17-producing CD4+ cells as well as a reduced number of IFN-γ − producing CD4+ cells and Foxp3-producing CD4+ cells. However, after the IL-27 treatment, these expression patterns were reversed with the exception of the IL-10-producing CD4+ cells (Figure 3A, B). The above findings suggest that IL-27 inhibits pulmonary fibrosis by regulating T lymphocyte differentiation in the spleen.Figure 3

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