Expression of Epstein–Barr virus‐induced gene 3 and other interleukin‐12‐related molecules by human intestinal epithelium

Egan, Laurence J.; Birkenbach, Mark; Eckmann, Lars; Kagnoff, Martin F.

doi:10.1111/j.1365-2567.2004.01895.x

Cited by 33 publications

(24 citation statements)

References 43 publications

(149 reference statements)

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“…However, according to recent reports, EBI3 is also expressed in other cell types, including intestinal epithelium and aortic smooth muscle cells (36,37). Our results suggested that epidermal keratinocytes as well as Treg express EBI3, and this expression was decreased in the SSc skin.…”

Section: Discussionsupporting

confidence: 41%

EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin

Kudo

Wang

Jinnin

et al. 2015

The Journal of Immunology

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IL-12 family cytokines are implicated in the pathogenesis of various autoimmune diseases, but their role in the regulation of extracellular matrix expression and its contribution to the phenotype of systemic sclerosis (SSc) remain to be elucidated. Among the IL-12 family members, IL-35 decreases type I collagen expression in cultured dermal fibroblasts. IL-35 consists of p35 and EBI3 subunits, and EBI3 alone could downregulate the protein and mRNA expression of type I or type III collagen in the presence or absence of TGF-β costimulation. We found that collagen mRNA stability was reduced by EBI3 via the induction of miR-4500. The IL-35 levels in the sera or on the surface of T cells were not altered in SSc patients, while EBI3 expression was decreased in the keratinocytes of the epidermis and regulatory T cells of the dermis in SSc skin compared with normal skin, which may induce collagen synthesis in SSc dermal fibroblasts. We also found that gp130, the EBI3 receptor, was expressed in both normal and SSc fibroblasts. Moreover, we revealed that EBI3 supplementation by injection into the skin improves mice skin fibrosis. Decreased EBI3 in SSc skin may contribute to an increase in collagen accumulation and skin fibrosis. Clarifying the mechanism regulating the extracellular matrix expression by EBI3 in SSc skin may lead to better understanding of this disease and new therapeutic strategies using ointment or microinjection of the subunit.

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Section: Discussionsupporting

confidence: 41%

EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin

Kudo

Wang

Jinnin

et al. 2015

The Journal of Immunology

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“…Compared with other IL-12-related cytokines, IL-27 differs in that its subunits are not covalently linked. Expression of EBI3 has been found in obligatory APCs, including dendritic cells (DCs) and macrophages, as well as in activated vascular endothelium, syncytiotrophoblasts, and intestinal epithelium (Coulomb-L'Hermine et al 2007;Maaser et al 2004). EBI3, secreted readily by itself, also forms an alternative biologically active heterodimer with IL-12p35, forming IL-35 (Collison et al 2007).…”

Section: Il-27 and Its Receptormentioning

confidence: 99%

Interleukin-27: Biological Properties and Clinical Application

Jankowski

Kopiński

Goc

2010

Arch. Immunol. Ther. Exp.

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Interleukin (IL)-27 is a novel cytokine secreted by stimulated antigen-presenting cells. Initial studies on the biology of IL-27 provided evidence for its role in the initiation of T(H)1 responses; however, subsequent work has indicated that IL-27 has broad inhibitory effects on T(H)1, T(H)2, and T(H)17 subsets of T cells as well as the expansion of inducible regulatory T cells. The involvement of IL-27 in the regulation of angiogenesis and antiviral response has also recently been reported. The aim of this review is to highlight the potential areas of IL-27 clinical application, especially the management of neoplastic and viral diseases as well as autoimmune disorders, including rheumatoid arthritis and multiple sclerosis. The review will also serve to elaborate on the molecular mechanisms involved in the expression of this cytokine and signaling from the IL-27 receptor.

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“…Reverse transcription and PCR were performed as described before. Primers and PCR conditions were used as described earlier (20). Experiments were performed three times, and representative results are shown.…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Expression of IL-12-related molecules in human intestinal microvascular endothelial cells is regulated by TLR3

Heidemann¹,

Rüther²,

Kebschull³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Members of the interleukin (IL)-12 family constitute subunits of IL-12, -23, and -27. These ILs represent pivotal mediators in the regulation of cell-mediated immune responses and in animal models of human inflammatory bowel disease. Recent work has suggested that intestinal endothelial cells might serve as a second line of defense in bacterial sensing of invading pathogens. The purpose of this study was to examine the production of IL-12 family members in intestinal endothelial cells (HIMEC). HIMEC were stimulated with proinflammatory agents (TNF-α, IFN-γ, IL-1β) and microbial antigens [LPS, lipoteichoic acid, peptidoglycan, CpG-DNA, flagellin, poly(I:C)]. Expression of IL-12 family members and of Toll-like receptor (TLR)3 in HIMEC was assessed by real-time RT-PCR, immunostaining, flow cytometry, and immunoblot analysis. HIMEC display an induction of Epstein-Barr virus-induced gene 3 (EBI3), IL-12p35, and IL-23p19, whereas no expression of IL-12p40 and IL-27p28 was detectable. The strongest induction was induced by proinflammatory factors known to utilize the NF-κB pathway, and expression of EBI3 and IL-23p19 was diminished by an NF-κB inhibitor. HIMEC display regulated expression of TLR3. Adhesion and transmigration assays showed proinflammatory responses after HIMEC stimulation. HIMEC are capable of producing IL-12 family members as a response to microbial stimuli. The TLR3 agonist, poly(I:C), was shown to enhance leukocyte adhesion in vitro in HIMEC. Our data suggest that the intestinal microvasculature is responsive to ligands of TLR3 expressed on intestinal endothelial cells, thereby adding to the regulation of adaptive immunity and leukocyte recruitment.

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Expression of Epstein–Barr virus‐induced gene 3 and other interleukin‐12‐related molecules by human intestinal epithelium

Cited by 33 publications

References 43 publications

EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin

EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin

Interleukin-27: Biological Properties and Clinical Application

Expression of IL-12-related molecules in human intestinal microvascular endothelial cells is regulated by TLR3

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