Bacillus Calmette-Guérin and TLR4 Agonist Prevent Cardiovascular Hypertrophy and Fibrosis by Regulating Immune Microenvironment

Liu, Yu Ying; Cai, Wenyu; Yang, Hong Zhen; Cui, Bing; Chen, Zhi Rong; Liu, Han Zhi; Yan, Jun; Wen, Ji; Yan, Hui; Xin, Bing; Yuan, Bin; Hua, Fang; Hu, Zhuo Wei

doi:10.4049/jimmunol.180.11.7349

Cited by 46 publications

(43 citation statements)

References 36 publications

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“…Although a number of studies have highlighted the differential regulatory roles for Th1 and Th2 responses in the pathogenesis of tissue fibrosis (15,31), it is unclear how the Th1/2 balance affects the progression of tissue fibrosis. Recent studies have indicated that autophagy acts as an immune effector mechanism against intracellular pathogens and functions to heal injured tissue and remove cellular debris.…”

Section: Discussionmentioning

confidence: 99%

Blocking IL-17A Promotes the Resolution of Pulmonary Inflammation and Fibrosis Via TGF-β1–Dependent and –Independent Mechanisms

Yang

et al. 2011

The Journal of Immunology

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327

269

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Pulmonary fibrosis is the pathologic basis for a variety of incurable human chronic lung diseases. IL-17A, a glycoprotein secreted from IL-17–producing cells, has recently been shown to be a proinflammatory cytokine involved in chronic inflammation and autoimmune disease. In this study, we report that IL-17A increased the synthesis and secretion of collagen and promoted the epithelial–mesenchymal transition in alveolar epithelial cells in a TGF-β1–dependent manner. Using in vivo fibrotic models, we found IL-17A expression to be elevated and IL-17A–associated signaling pathways to be activated in fibrotic lung tissues. Neutralization of IL-17A in vivo promoted the resolution of bleomycin-induced acute inflammation, attenuated pulmonary fibrosis, and increased survival. Additionally, IL-17A antagonism inhibited silica-induced chronic inflammation and pulmonary fibrosis. Targeting IL-17A resulted in a shift of the suppressive immune response in fibrotic lung tissue toward a Th1-type immune response, and it effectively induced autophagy, which promoted the autophagic degradation of collagen and autophagy-associated cell death. Moreover, IL-17A was found to attenuate the starvation-induced autophagy, and autophagy modulators regulated collagen degradation in the alveolar epithelial cells in a TGF-β1–independent manner. Administration of 3-methylamphetamine, an autophagy inhibitor, reversed the therapeutic efficacy of IL-17A antagonism in pulmonary fibrosis. Our studies indicate that IL-17A participates in the development and progression of pulmonary fibrosis in both TGF-β1–dependent and –independent manners and that the components of the IL-17A signaling pathway are potential therapeutic targets for the treatment of fibroproliferative lung diseases.

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Section: Discussionmentioning

confidence: 99%

Blocking IL-17A Promotes the Resolution of Pulmonary Inflammation and Fibrosis Via TGF-β1–Dependent and –Independent Mechanisms

Yang

et al. 2011

The Journal of Immunology

Self Cite

327

269

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“…39 It has been shown that LPS and CysLT induce the activation of ERK1/2 and p38. 41,42 Taking this into account, we decided to analyse the activation of ERK1/2 and p38 MAPK. Western blots of lysates from DCs cultured without or with LPS (1 lg/ml) for 30 min at 37°w ere incubated in the presence or not of LTC 4 (10 -8…”

Section: Leukotriene C 4 Activates Mapk Depending On the Activation Smentioning

confidence: 99%

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Álvarez¹,

Amaral²,

Langellotti³

et al. 2011

Immunology

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Summary Leukotriene C4 is an important mediator in the development of inflammatory reactions and ischaemia. Previous studies have shown that leukotriene C4 is able to modulate the function of dendritic cells (DCs) and induce their chemotaxis from skin to lymph node. In this study, we decided to evaluate the modulation exerted by leukotriene C4 on DCs, depending on their status of activation. We showed for the first time that leukotriene C4 stimulates endocytosis both in immature and lipopolysaccharide (LPS) ‐activated DCs. Moreover, it suppressed the interleukin‐12p70 (IL‐12p70) release, but induces the secretion of IL‐23 by DCs activated with LPS and promotes the expansion of T helper type 17 (Th17) lymphocytes. Furthermore, blocking the release of IL‐23 reduced the percentages of CD4+ T cells producing IL‐17 in a mixed lymphocyte reaction. Ours results suggest that leukotriene C4 interferes with the complete maturation of inflammatory DCs in terms of phenotype and antigen uptake, while favouring the release of IL‐23, the main cytokine involved in the maintenance of the Th17 profile.

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“…Human breast or colon cancer tissue microarray slides (US Biomax) were detected as previously described (27).…”

Section: Tissue Microarray Slides and Immunohistochemistrymentioning

confidence: 99%

DEDD Interacts with PI3KC3 to Activate Autophagy and Attenuate Epithelial–Mesenchymal Transition in Human Breast Cancer

et al. 2012

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Epithelial-to-mesenchymal transition (EMT), a crucial developmental program, contributes to cancer invasion and metastasis. In this study, we show that death-effector domain-containing DNA-binding protein (DEDD) attenuates EMT and acts as an endogenous suppressor of tumor growth and metastasis. We found that expression levels of DEDD were conversely correlated with poor prognosis in patients with breast and colon cancer. Both in vitro and in vivo, overexpression of DEDD attenuated the invasive phenotype of highly metastatic cells, whereas silencing of DEDD promoted the invasion of nonmetastatic cells. Via direct interaction with the class III PI-3-kinase (PI3KC3)/Beclin1, DEDD activated autophagy and induced the degradation of Snail and Twist, two master regulators of EMT. The DEDD-PI3KC3 interaction led to stabilization of PI3KC3, which further contributed to autophagy and the degradation of Snail and Twist. Together, our findings highlight a novel mechanism in which the intracellular signaling protein DEDD functions as an endogenous tumor suppressor. DEDD expression therefore may represent a prognostic marker and potential therapeutic target for the prevention and treatment of cancer metastasis. Cancer Res; 72(13); 3238-50. Ó2012 AACR.

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Bacillus Calmette-Guérin and TLR4 Agonist Prevent Cardiovascular Hypertrophy and Fibrosis by Regulating Immune Microenvironment

Cited by 46 publications

References 36 publications

Blocking IL-17A Promotes the Resolution of Pulmonary Inflammation and Fibrosis Via TGF-β1–Dependent and –Independent Mechanisms

Blocking IL-17A Promotes the Resolution of Pulmonary Inflammation and Fibrosis Via TGF-β1–Dependent and –Independent Mechanisms

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

DEDD Interacts with PI3KC3 to Activate Autophagy and Attenuate Epithelial–Mesenchymal Transition in Human Breast Cancer

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