Suppression of Th1 cytokine production by a peptide derived from C4b

Takeda, Yuji; Kaneda, Kenta; Jimma, Fumie; Shiobara, Noriyuki; Saniabadi, Abbi R.; Wakabayashi, Ichiro

doi:10.1007/s00011-013-0650-z

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Chronic colitis accompanied by a large accumulation of T helper cell 1 (Th1), Th2 and Th17 promotes neoplastic risk, whereas excessive immunosuppression regulated by Treg cells enhances the survival of tumor cells [ 1 , 10 , 11 ]. Many researchers have reported that excessive Th1 cells in intestinal mucosa are the main reason for chronic colitis; these cells produce interferon (IFN)-γ and interleukin-2 (IL-2) [ 12 , 13 ]. Meanwhile, CAC was also characterized as a Th2/Th17 disease accompanied by overproduction of cytokines such as IL-4, IL-5, IL-13 and IL-17 [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer

et al. 2015

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IntroductionPrevious studies have produced controversial results regarding whether mesenchymal stem cells (MSCs) promote or inhibit tumor development. Given the dual role of MSCs in inflammation and cancer, in this study the colitis-associated colorectal cancer (CAC) model was used to examine whether umbilical cord tissue-derived MSCs could prevent neoplasm by inhibiting chronic inflammation.MethodsMSCs were obtained and identified using flow cytometry. Colitis-associated colorectal cancer model was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) and MSCs were injected intravenously twice. Levels of immune cells in mesenteric lymph node including regulatory T (Treg) cells were detected using flow cytometry. Naïve T cells and Jurkat cells were co-cultured with MSCs and the effect of MSCs on Treg cells differentiation was evaluated.ResultsAfter injection through tail vein, MSCs could migrate to colon and suppress colitis-related neoplasm. This tumor suppressive effect was characterized by longer colon length, decreased tumor numbers and decreased expression of Ki-67. Moreover, MSCs alleviated the pathology of inflammation in the colitis stage of CAC model and inhibited inflammation cytokines both in colon and serum. Furthermore, Treg cells were accumulated in mesenteric lymph node of MSCs-treated mice while the percentage of T helper cells 2 (Th2) and Th17 were not changed. Of note, MSCs secreted transforming growth factor-β (TGF-β) enhanced the induction of Treg cells from naïve T cells. The conditioned medium of MSCs also activated Smad2 signaling, which has been reported to regulate Treg cells.ConclusionsThese results proved that MSCs could migrate to colon tissues and induce the differentiation of Treg cells via Smad2 as so to inhibit the colitis and suppress the development of CAC.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer

et al. 2015

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“…The statistical significances were analyzed with Wilcoxon signed-rank test (two-tailed). The significant differences are shown as *, P < .05; and ns, no-significant (n = 8) generated by CA beads suppressed inflammatory responses, 17,20 suggesting the correlation of C4a generation with the anti-inflammatory response during GMA.…”

Section: Discussionmentioning

confidence: 99%

Physiological heating augments the anti‐inflammatory reactions during granulocyte/monocyte apheresis: A in vitro study

et al. 2020

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Granulocyte and monocyte adsorptive apheresis (GMA), an effective therapy for inflammatory disorders, exerts an anti-inflammatory influence by utilizing the biological reaction between blood and cellulose acetate (CA) beads, which are the carriers of the GMA column. Although the biological reaction has an optimum temperature, blood contacts the CA beads below body temperature as GMA is performed in an extracorporeal circulation system. We investigated various soluble factors in blood treated with CA beads at 25 C and 37 C. Here, the optimal temperature for IL-1 receptor antagonist (IL-1ra) release induced by CA beads was 37 C, and IL-6 production from monocytic cells was inhibited by the addition of plasma prepared from the CA bead-treated blood at 37 C, rather than at 25 C. These results indicated that physiological heating of the apheresis carrier augmented the anti-inflammatory reaction in vitro. Thus, heating during GMA may be a new approach for augmenting clinical efficacy.

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“…CBA Analysis-Cytokines in the cell culture supernatants were analyzed by CBA (BD Biosciences) as described previously (29). A customized set of fluorescent anti-cytokine multiplex microbeads was obtained together with recombinant standards with which to prepare a standard curve for each cytokine.…”

Section: Methodsmentioning

confidence: 99%

Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 (Ape1/Ref-1) Modulates Antigen Presenting Cell-mediated T Helper Cell Type 1 Responses

Akhter

Takeda

Nara

et al. 2016

Journal of Biological Chemistry

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Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1) is a multifunctional protein possessing DNA repair, redox control, and transcriptional regulatory activities. Although Ape1/Ref-1 plays multiple roles in the immune system, its functions in helper T (Th) cell activation and differentiation are largely unknown. In this study, the function of Ape1/Ref-1 in Th cell activation was analyzed using an Ape1/Ref-1 redox-specific inhibitor, E3330. When splenocytes from OT-II mice, which are ovalbumin (OVA)-specific T-cell receptor transgenic mice, were activated with OVA in the presence of E3330, the induction of IFN-γ-producing OT-II T cells was significantly increased. In contrast, E3330 did not enhance IFN-γ production from plate-bound anti-CD3 antibody-stimulated CD4 T cells in the absence of antigen presenting cells (APCs). Furthermore, E3330-pretreated and OVA-pulsed APCs also enhanced the IFN-γ production from OT-II T cells. These results suggested that E3330 enhances Th1 responses by modifying APC function. E3330 did not alter the surface expression of MHC-II or the co-stimulatory molecules CD80 and CD86 on APCs. On the other hand, E3330 up-regulated the IL-12 p35 and p40 gene expression, and IL-12 surface retention, but decreased the IL-12 secretion from Toll-like receptor (TLR) ligand-stimulated APCs. These results were confirmed with Ape1/Ref-1 knockdown experiments. Taken together, our findings indicated that the suppression of Ape1/Ref-1 redox function leads to an increased cell surface retention of IL-12 and enhances Th1 responses. This is the first study to demonstrate that Ape1/Ref-1 modulates the IL-12 production and secretion from APCs and controls Th1 immune responses.

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Suppression of Th1 cytokine production by a peptide derived from C4b

Abstract: The amino acid sequence described above is suggested to be the active site in C4b for the inhibition of Th1 cytokine production. These results should contribute to the development of new drugs suppressing autoimmune responses.

Cited by 7 publications

References 18 publications

Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer

Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer

Physiological heating augments the anti‐inflammatory reactions during granulocyte/monocyte apheresis: A in vitro study

Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 (Ape1/Ref-1) Modulates Antigen Presenting Cell-mediated T Helper Cell Type 1 Responses

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