Systems biology of IL-6, IL-12 family cytokines

Dittrich, Anna; Hessenkemper, Wiebke; Schaper, Fred

doi:10.1016/j.cytogfr.2015.07.002

Cited by 37 publications

(29 citation statements)

References 91 publications

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“…IL-6 could be produced by macrophages and the activated T lymphocytes [33]. Macrophages were also an important source of IL-1β and G-CSF [24, 34].…”

Section: Resultsmentioning

confidence: 99%

IL-35 induces N2 phenotype of neutrophils to promote tumor growth

Zou

Qin

et al. 2017

Oncotarget

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IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils. IL-35 stimulated macrophages to secrete proinflammatory cytokines IL-1β and IL-6. IL-1β stimulated γδ T cells to produce IL-17, which in turn increased the production of G-CSF. By increasing the expression of G-CSF and IL-6, IL-35 could up-regulate the expression of MMP-9 and Bv8, and down-regulate TRAIL expression in neutrophils, thus augmenting the proangiogenic function of neutrophils. Moreover, G-CSF/IL-6 induced the enhanced activation of STAT3 and ERK pathways in neutrophils, thus increasing the expression of iNOS to suppress T cell activation. Our findings suggest that IL-35 can promote tumor progression by functioning as an up-stream cytokine to promote cancer-associated inflammation and control neutrophil polarization. Targeting IL-35 might be an important approach for designing new strategy of tumor therapy.

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“…IL-6 could be produced by macrophages and the activated T lymphocytes [33]. Macrophages were also an important source of IL-1β and G-CSF [24, 34].…”

Section: Resultsmentioning

confidence: 99%

IL-35 induces N2 phenotype of neutrophils to promote tumor growth

Zou

Qin

et al. 2017

Oncotarget

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“…During recently years, the benefits of GM-CSF application have been demonstrated to protect lung injury in sepsis37. As for IL-6, it is a multifunctional cytokine involved in the regulation of complex cellular processes such as proliferation and differentiation, and act as a key player during immune and inflammation response38. Recently, IL-6 is found to promote survival of human CD11b + peripheral blood mononuclear cells and induce M2-type macrophage polarization39.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Acute Lung Injury Mice

Zhu

Xia

et al. 2017

Sci Rep

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The incidence and mortality of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are still very high, but stem cells show some promise for its treatment. Here we found that intratracheal administration of human umbilical cord-mesenchymal stem cells (UC-MSCs) significantly improved survival and attenuated the lung inflammation in lipopolysaccharide (LPS)-induced ALI mice. We also used the proteins-chip and bioinformatics to analyze interactions between UC-MSCs treatment and immune-response alternations of ALI mice. Then we demonstrated that UC-MSCs could inhibit the inflammatory response of mouse macrophage in ALI mice, as well as enhance its IL-10 expression. We provide data to support the concept that the therapeutic capacity of UC-MSCs for ALI was primarily through paracrine secretion, particularly of prostaglandin-E2 (PGE2). Furthermore, we showed that UC-MSCs might secrete a panel of factors including GM-CSF, IL-6 and IL-13 to ameliorate ALI. Our study suggested that UC-MSCs could protect LPS-induced ALI model by immune regulation and paracrine factors, indicating that UC-MSCs should be a promising strategy for ALI/ARDS.

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“…NO is involved in various biological reactions including vasorelaxation, inhibition of platelet aggregation, neurotransmission, inflammation, and immunoregulation [51, 52]. Therefore, identifying new agents capable of lowering the production of this proinflammatory agent is regarded as an essential requirement for the alleviation of a number of inflammation-related disorders attributed to macrophage activation [53]. Similarly, COX and PLA 2 are key enzymes in the synthesis of inflammatory prostaglandins which contributes to pathogenesis of various inflammatory diseases, edema, angiogenesis, invasion, and growth of tumor.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory and antioxidative effects of six pentacyclic triterpenes isolated from the Mexican copal resin of Bursera copallifera

Romero-Estrada

Maldonado-Magaña

González-Christen

et al. 2016

BMC Complement Altern Med

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Background Bursera copallifera (Burseraceae) releases a resin known as “copal ancho” which has been used, since pre-Colombian times, as ceremonially burned incense and to treat tooth ache, tumors, arthritis, cold, cough, and various inflammatory conditions; however, its anti-inflammatory potential is poorly studied. The aim of the present study was to isolate, quantify, and to investigate the anti-inflammatory activity of triterpene compounds isolated from the copal resin of B. copallifera.MethodsThe constituents present in the total resin of B. copallifera were obtained by successive chromatographic procedures, and quantitative analysis was performed by High Performance Liquid Chromatography (HPLC). Anti-inflammatory effects of the isolated triterpenes were investigated to determine their inhibitory effects on phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema in mice, viability and nitric oxide (NO) production inhibition on lipopolysaccharide (LPS)-activated RAW 264.7 macrophages, and inhibition of cyclooxygenase (COX)-1, COX-2 and secretory Phospholipase A2 (sPLA2) activities in vitro.ResultsQuantitative phytochemical analysis of the copal resin showed the presence of six pentacyclic triterpenes of which, 3-epilupeol (59.75 % yield) and α-amyrin (21.1 % yield) are the most abundant. Among the isolated triterpenes, 3-epilupeol formiate (Inhibitory Concentration 50 % (IC50) = 0.96 μmol), α.amyrin acetate (IC50 = 1.17 μmol), lupenone (IC50 = 1.05 μmol), and 3-epilupeol (IC50 = 0.83 μmol) showed marked inhibition of the edema induced by TPA in mice. α-amyrin acetate and 3-epilupeol acetate, at 70 μM, also inhibited the activity of COX-2 by 62.85 and 73.28 % respectively, while α-amyrin and 3-epilupeol were the best inhibitors of the production of NO in LPS-activated RAW 264.7 cells with IC50 values of 15.5 and 8.98 μM respectively, and did not affected its viability. All compounds moderately inhibited the activity of PLA2.ConclusionsThis work supports the folk use of B. copallifera and provides the basis for future investigations about the therapeutic use of this resin in treating inflammation.

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Systems biology of IL-6, IL-12 family cytokines

Cited by 37 publications

References 91 publications

IL-35 induces N2 phenotype of neutrophils to promote tumor growth

IL-35 induces N2 phenotype of neutrophils to promote tumor growth

Therapeutic Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Acute Lung Injury Mice

Anti-inflammatory and antioxidative effects of six pentacyclic triterpenes isolated from the Mexican copal resin of Bursera copallifera

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