IL-27 Regulates IL-18 Binding Protein in Skin Resident Cells

Wittmann, Miriam; Doble, Rosella; Bachmann, Michael; Pfeilschifter, Josef; Werfel, Thomas; Mühl, Heiko

doi:10.1371/journal.pone.0038751

Cited by 43 publications

(34 citation statements)

References 63 publications

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“…5C and Supplementary Fig. S5D), as reported for other IL-27-sensitive cell types (33,34). In addition, Western blot analysis showed that STAT1 was constitutively tyrosine-phosphorylated in cells isolated from ascites ex vivo and was further activated by in vitro treatment with IL-27 (Fig.…”

Section: Ifn-g and Il-27 Upregulate Il-18bp In Human Eoc Cell Linessupporting

confidence: 77%

“…This is not the case for IFN-g, in view of its species specificity. Because other cytokines, which are elevated in the ascites of EOC failed to induce IL-18BP expression in vitro, we focused on IL-27, which was recently shown to stimulate IL-18BP expression in human keratinocytes (33).…”

Section: Discussionmentioning

confidence: 99%

“…On one hand, IL-27 has proinflammatory effects through the induction of CXCL10 in macrophages in inflammatory skin disorders (43). However, IL-27 may limit the proinflammatory and immune-enhancing activities of IL-18 in the skin through IL-18BP induction (33) and may dampen autoimmunity, as Il27 À/À mice were more susceptible to experimental autoimmune encephalomyelitis (44). Here, we show that IL-27 induces the expression of IL-18BP mRNA and protein in human EOC cell lines in culture and activates STAT1 signaling in these cells, whereas IL-35, another EBI3-containing cytokine (30), was inactive.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The IL-18 Antagonist IL-18–Binding Protein Is Produced in the Human Ovarian Cancer Microenvironment

Carbotti

Barisione

Orengo

et al. 2013

Clinical Cancer Research

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Purpose: Interleukin (IL)-18 is an immune-enhancing cytokine, which induces IFN-g production, T-helper 1 responses, and antitumor effects. In turn, IFN-g stimulates IL-18-binding protein production, which blocks IL-18 activity. In view of the potential use of IL-18 in epithelial ovarian cancer (EOC) immunotherapy, here, we studied IL-18BP expression and its regulation by cytokines in EOC cells in vitro and in vivo.Experimental Design: Expression and production of IL-18BP in EOC cell lines, primary ovarian carcinomas, and the corresponding normal tissues, patients' serum, and ascites were investigated by immunochemistry, ELISA, screening of gene expression profiles, and reverse-transcription PCR.Results: Analysis of gene expression profiles revealed that IL18BP mRNA is increased in EOC tumors compared with normal ovary cells. Release of IL-18BP was detectable in EOC sera and to a greater extent in the ascites, indicating production at the tumor site. Indeed, immunochemical analyses on cells isolated from the ascites and on tumor sections indicated that IL-18BP is expressed in both tumor cells and tumor-associated leukocytes, which displayed a CD3 À CD20EOC cell lines do not constitutively express IL-18BP. However, its release is inducible both by IFN-g stimulation in vitro and by xenotransplantation of EOC cells in immune-deficient mice, suggesting a role for the microenvironment. In vitro experiments and immunochemistry indicated that IL-27 is also involved in IL-18BP upregulation in EOC cell lines and primary cells through STAT1 activation. Together, these data indicate that IL-18BP, which is produced in EOC in response to microenvironmental factors, may inhibit endogenous or exogenous IL-18 activity.

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Section: Ifn-g and Il-27 Upregulate Il-18bp In Human Eoc Cell Linessupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The IL-18 Antagonist IL-18–Binding Protein Is Produced in the Human Ovarian Cancer Microenvironment

Carbotti

Barisione

Orengo

et al. 2013

Clinical Cancer Research

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“…Little is known about the role of IL-27 in murine models of skin disease, but in humans with chronic eczema, keratinocytes express IL-27 and respond to IL-27, which triggers increased MHC class I www.annualreviews.org • The Immunobiology of IL-27 429 expression, the production of β-defensin-2, and the production of the chemokine CXCL10 (195)(196)(197). In human psoriasis, IL-27 has been associated with disease progression (197)(198)(199); in patients with systemic sclerosis, a condition characterized by the abnormal accumulation of collagen and vascular damage in the skin, elevated levels of IL-27Rα are expressed in fibroblasts, and IL-27 promotes fibroblast proliferation and the production of collagen (200).…”

Section: Il-27 At Barrier Surfacesmentioning

confidence: 99%

The Immunobiology of Interleukin-27

Yoshida

Hunter

2015

Annu. Rev. Immunol.

364

433

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Interleukin-27 (IL-27) is a cytokine with strikingly diverse influences on the immune response. Although it was initially linked with the development of Th1 responses, it is now recognized as a potent antagonist of different classes of inflammation through its ability to directly modify CD4(+) and CD8(+) T cell effector functions, to induce IL-10, and to promote specialized T regulatory cell responses. Although this aspect of IL-27 biology has provided insights into how the immune system prevents hyperactivity in the setting of infectious and autoimmune inflammation, in vaccination and cancer models the stimulatory effects of IL-27 on CD8(+) T cell function appear prominent. Additionally, associations between IL-27 and antibody-mediated disease have led to an interest in defining the impact of IL-27 on innate immunity and humoral responses in different disease states. The maturation of this literature has been accompanied by attempts to translate these findings from experimental models into human diseases and by efforts to define where IL-27 might represent a viable therapeutic target.

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“…In addition, IL-18BP mRNA is also detected in the intestinal tract and in the prostate [73]. In human epithelial cell lines, IFN-c stimulates the production and release of IL-18BPa [75,76] and IL-27 stimulates the production of IL-18BP by skin resident cells [77]. Endothelial cells and monocyte/macrophages represent also important sources of IL-18BP.…”

Section: Il-18bpmentioning

confidence: 99%