Interleukin 18 (IL-18) as a target for immune intervention.

2016 ◽  
Vol 63 (1) ◽  
Author(s):  
Sebastian Wawrocki ◽  
Magdalena Druszczynska ◽  
Magdalena Kowalewicz-Kulbat ◽  
Wieslawa Rudnicka
Keyword(s):  
Surface Expression ◽  
Dependent Manner ◽  
Interleukin 18 ◽  
T Helper ◽  
Immune Intervention ◽  
Inhibitory Protein ◽  
Ifn Gamma ◽  
Potent Inducer ◽  
Cell Responses ◽  
Th 1

Interleukin 18 (IL-18) is a pleiotropic cytokine involved in the regulation of innate and acquired immune response. In the milieu of IL-12 or IL-15, IL-18 is a potent inducer of IFN-gamma in natural killer (NK) cells and CD4 T helper (Th) 1 lymphocytes. However, IL-18 also modulates Th2 and Th17 cell responses, as well as the activity of CD8 cytotoxic cells and neutrophils, in a host microenvironment-dependent manner. It is produced by various hematopoietic and nonhematopoietic cells, including dendritic cells and macrophages. In an organism, bioactivity of the cytokine depends on the intensity of IL-18 production, the level of its natural inhibitory protein - IL-18BP (IL-18 binding protein) and the surface expression of IL-18 receptors (IL-18R) on the responding cells. This review summarizes the biology of the IL-18/IL-18BP/IL-18R system and its role in the host defense against infections. The prospects for IL-18 application in immunotherapeutic or prophylactic interventions in infectious and non-infectious diseases are discussed.

Molecular Characterization of the Cannabinoid-Mediated Migration of Monocytes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3878-3878
Author(s):  
In-Woo Park ◽  
Appakkudal R. Anand ◽  
Jerome E. Groopman
Keyword(s):  
Intracellular Signaling ◽  
Cannabinoid Receptors ◽  
Rho Kinase ◽  
Surface Expression ◽  
Dependent Manner ◽  
Monocytic Differentiation ◽  
Monocytic Cells ◽  
Potent Inducer ◽  
Monocyte Migration ◽  
Enhanced Secretion

Abstract 2-Arachidonoylglycerol (2-AG), an endogenous ligand for the cannabinoid receptors CB1 and CB2, functions as a chemokine for monocyte migration. However, the molecular mechanism of its chemotactic effects is not clear. We found, consistent with previous data, that 2-AG induces the migration of differentiated but not undifferentiated monocytic cells in a dose-dependent manner. We first asked whether the expression of cannabinoid receptors changed during monocytic differentiation. Treatment with 1,25-(OH)2vitamin D3, a potent inducer of monocyte differentiation, or with 2-AG did not alter the surface expression of the CB1 and CB2 receptors, indicating that signaling downstream of receptor ligation accounted for the observed effect on monocyte migration. In addition, treatment of differentiated monocytic cells with inhibitors for adenyl cyclase and rho kinase blocked the 2-AG-mediated migration, directly implicating these signaling molecules in monocyte motility. Upon eliminating the concentration gradient of 2-AG, the motility of the cells from the upper to lower compartment was sharply reduced, but not completely abrogated. This suggested that the chemotactic effect may not fully explain the observed change in cell migration. Of note, treatment of monocytes with 2-AG resulted in an enhanced secretion of the chemokines MCP-1 and IL-8. Moreover, exposure of the cells to 2-AG inhibited their migration towards MCP-1, while exposure to MCP-1 did not alter migration toward 2-AG. Taken together, our findings demonstrate that intracellular signaling cascades as well as induction of chemokine secretion contribute to the cannabinoid-mediated migration of monocytes.

scholarly journals Interferon-gamma upregulates interleukin-8 gene expression in human monocytic cells by a posttranscriptional mechanism

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 537-542
Author(s):  
MC Bosco ◽  
GL Gusella ◽  
I Espinoza-Delgado ◽  
DL Longo ◽  
L Varesio
Keyword(s):  
Gene Expression ◽  
Interferon Gamma ◽  
Mononuclear Phagocytes ◽  
Interleukin 8 ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Monocytic Cells ◽  
Ifn Gamma ◽  
Potent Inducer

Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is produced in response to several stimuli. Because monocytic cells are important producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent inducer of activation and differentiation of mononuclear phagocytes, affected IL-8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA expression that was upregulated by IFN-gamma in a dose- and time- dependent manner and via a protein-synthesis-dependent process in the human monocytic cell line U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on experiments showed that the IL- 8 gene was transcriptionally active in control cells and that IFN-gamma did not enhance the transcriptional activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the mRNA and, therefore, controlled primarily at a posttranscriptional level. These results represent the first evidence that IFN-gamma upregulates IL-8 gene expression in cells of the monocytic lineage, and show the involvement of posttranscriptional mechanisms in the induction of IL-8 mRNA.

scholarly journals Interferon-gamma upregulates interleukin-8 gene expression in human monocytic cells by a posttranscriptional mechanism

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 537-542 ◽  
Author(s):  
MC Bosco ◽  
GL Gusella ◽  
I Espinoza-Delgado ◽  
DL Longo ◽  
L Varesio
Keyword(s):  
Gene Expression ◽  
Interferon Gamma ◽  
Mononuclear Phagocytes ◽  
Interleukin 8 ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Monocytic Cells ◽  
Ifn Gamma ◽  
Potent Inducer

Abstract Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is produced in response to several stimuli. Because monocytic cells are important producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent inducer of activation and differentiation of mononuclear phagocytes, affected IL-8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA expression that was upregulated by IFN-gamma in a dose- and time- dependent manner and via a protein-synthesis-dependent process in the human monocytic cell line U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on experiments showed that the IL- 8 gene was transcriptionally active in control cells and that IFN-gamma did not enhance the transcriptional activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the mRNA and, therefore, controlled primarily at a posttranscriptional level. These results represent the first evidence that IFN-gamma upregulates IL-8 gene expression in cells of the monocytic lineage, and show the involvement of posttranscriptional mechanisms in the induction of IL-8 mRNA.

scholarly journals Early Secreted Antigen ESAT-6 of Mycobacterium tuberculosis Promotes Protective T Helper 17 Cell Responses in a Toll-Like Receptor-2-dependent Manner

2011 ◽  
Vol 7 (11) ◽  
pp. e1002378 ◽  
Author(s):  
Samit Chatterjee ◽  
Ved Prakash Dwivedi ◽  
Yogesh Singh ◽  
Imran Siddiqui ◽  
Pawan Sharma ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
T Helper ◽  
T Helper 17 ◽  
Cell Responses ◽  
T Helper 17 Cell ◽  
Toll Like Receptor 2

scholarly journals Lymphokine gene expression in vivo is inhibited by cyclosporin A.

1990 ◽  
Vol 171 (2) ◽  
pp. 533-544 ◽  
Author(s):  
A Granelli-Piperno
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cyclosporin A ◽  
Dependent Manner ◽  
Ifn Gamma ◽  
Cell Responses ◽  
Dose Dependent ◽  
In Vivo Administration

Murine T cells were stimulated in vivo by administering allogeneic cells or mitogens into the foot pads and then examining the draining popliteal lymph nodes. Allogeneic spleen cells induced the expression of IL2 and IFN-gamma mRNAs in a time- and dose-dependent manner. Induction of these transcripts also was detected after administration of Con A and anti-CD3 mAb. An increase in DNA-synthesizing cells was observed by 48 h, and these were shown to be T cells because of their sensitivity to anti-Thy-1 but not anti-B220 mAb and complement, and because of their localization to the T-dependent areas of the lymph node. The in vivo administration of cyclosporin A (CSA) reduced several of these T cell responses. The level of DNA synthesis and the frequency of cells synthesizing DNA were decreased by approximately 75%, while the induction of IL-2 responsiveness was not substantially diminished. IL-2 and IFN-gamma transcripts were inhibited at least 70-90%, as determined by Northern blot and in situ hybridization. Although the inhibition by CSA was not as complete in animals as observed previously in tissue culture, our findings indicate that in both systems, a major site of action of CSA is to inhibit T cell growth by inhibiting lymphokine production.

scholarly journals CD8− DCs induce IL-12–independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS

2007 ◽  
Vol 204 (7) ◽  
pp. 1525-1531 ◽  
Author(s):  
Dimitris Skokos ◽  
Michel C. Nussenzweig
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Toll Like Receptor ◽  
T Helper ◽  
Cell Responses ◽  
Ligand Expression ◽  
Th 1 ◽  
Dependent Mechanism

Toll-like receptor (TLR) ligation is believed to skew T cell responses toward T helper (Th)1 differentiation by inducing interleukin (IL)-12 secretion by CD8+ dendritic cells (DCs). However, TLR-dependent Th1 responses occur in the absence of IL-12. To determine how DCs induce Th1 differentiation in the absence of IL-12, we examined the response of IL-12–deficient DCs to bacterial lipopolysaccharide (LPS). We find that LPS activates MyD88-dependent Delta 4 Notch-like ligand expression by CD8− DCs, and that these cells direct Th1 differentiation by an IL-12–independent and Notch-dependent mechanism in vitro and in vivo. Thus, activation of the two DC subsets by TLR4 leads to Th1 responses by two distinct MyD88-dependent pathways.

A polysaccharide from natural Cordyceps sinensis regulates the intestinal immunity and gut microbiota in mice with cyclophosphamide-induced intestinal injury

2021 ◽  
Author(s):  
Shuping Chen ◽  
Junqiao Wang ◽  
Qiuyue Fang ◽  
Nan Dong ◽  
Qingying Fang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Injury ◽  
Cordyceps Sinensis ◽  
Th2 Cells ◽  
Intestinal Immunity ◽  
T Helper ◽  
Th 1 ◽  
Immunosuppressed Mice

A polysaccharide from Cordyceps sinensis (NCSP) was reported to attenuate intestinal injury and regulate balance of T helper (Th)1/Th2 cells in immunosuppressed mice. However, whether it influences Th17 and regulatory...

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