Regulation of Interferon‐γ During Innate and Adaptive Immune Responses

Schoenborn, Jamie; Wilson, Christopher

doi:10.1016/s0065-2776(07)96002-2

Cited by 1,430 publications

(1,111 citation statements)

References 281 publications

Supporting

Mentioning

1,052

Contrasting

Unclassified

Order By: Relevance

“…In humans, IFNγ is encoded by the IFNG gene (Gray et al, 1982). This interferon, which early in its history was known as immune interferon, was first reported in 1970 (Schroder et al, 2004;Schoenborn et al, 2007). Our data demonstrated that overexpression of GOLPH2 in gastric cancer SGC7901 cells significantly reduced the secretion of the Th1-type cytokines TNF-α and IFN-γ from lymphocytes.…”

Section: Discussionmentioning

confidence: 62%

Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

Tang¹,

Ji²,

Tang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Golgi phosphoprotein 2 (GOLPH2) is a very important biomarker in a variety of diseases. Its biological function is not clear, particularly in gastric cancer. To investigate the role of GOLPH2 in human gastric cancer, and determine its effect on the Th1 lymphocyte response, its expression and that of IL-12A were measured by real-time PCR and immunohistochemistry. The relationship between GOLPH2 and IL-12A was analysed statistically. The effect of GOLPH2 on the Th1 lymphocyte response was investigated with an in vitro co-culture system. The results showed that in human gastric cancer, the expression of GOLPH2 was significantly higher and the expression of IL-12A was lower than in normal gastric mucosal tissues, and the expression levels of GOLPH2 and IL-12A were negatively correlated. In addition, obvious down-regulation of the Th1 response was observed when lymphocytes were co-cultured with gastric cancer SGC7901 cells over-expressing GOLPH2. GOLPH2 down-regulated the expression of IL-12A, and inhibited the expression of TNF-α and IFN-γ. The results indicated that GOLPH2 down-regulates the Th1 response via suppression of IL-12A in human gastric cancer, and this might provide a target for the prevention and treatment.

show abstract

Section: Discussionmentioning

confidence: 62%

Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

Tang¹,

Ji²,

Tang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…1E). IFN-γ is produced mainly by T cells and NK cells in response to cytokines, including IL-12 and IL-23 (37). The reduced production of IL-12 and IL-23 from Brd4-deficient macrophages might affect the responses from T and NK cells, leading to reduced IFN-γ production.…”

Section: Discussionmentioning

confidence: 99%

Brd4 modulates the innate immune response through Mnk2–eIF4E pathway-dependent translational control of IκBα

Bao

Chen

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Bromodomain-containing factor Brd4 has emerged as an important transcriptional regulator of NF-κB-dependent inflammatory gene expression. However, the in vivo physiological function of Brd4 in the inflammatory response remains poorly defined. We now demonstrate that mice deficient for Brd4 in myeloid-lineage cells are resistant to LPS-induced sepsis but are more susceptible to bacterial infection. Gene-expression microarray analysis of bone marrow-derived macrophages (BMDMs) reveals that deletion of Brd4 decreases the expression of a significant amount of LPS-induced inflammatory genes while reversing the expression of a small subset of LPS-suppressed genes, including MAP kinase-interacting serine/ threonine-protein kinase 2 (Mknk2). Brd4-deficient BMDMs display enhanced Mnk2 expression and the corresponding eukaryotic translation initiation factor 4E (eIF4E) activation after LPS stimulation, leading to an increased translation of IκBα mRNA in polysomes. The enhanced newly synthesized IκBα reduced the binding of NF-κB to the promoters of inflammatory genes, resulting in reduced inflammatory gene expression and cytokine production. By modulating the translation of IκBα via the Mnk2-eIF4E pathway, Brd4 provides an additional layer of control for NF-κB-dependent inflammatory gene expression and inflammatory response.T he inducible transcription factor NF-κB plays a key role in regulating the inflammatory and immune responses in mammals (1, 2). The prototypical NF-κB complex, the heterodimer of p50 and RelA, is sequestered in the cytoplasm by its assembly with its inhibitor IκBα (1, 2). Upon stimulation, IκB kinase complex is activated and phosphorylates IκBα, leading to the degradation of IκBα, the nuclear translocation of NF-κB complex, and the activation of NF-κB target genes (1-3). Importantly, one of NF-κB target genes is its inhibitor, IκBα. The resynthesized IκBα enters the nucleus, where it removes the NF-κB from the DNA and terminates activated NF-κB (1, 2, 4). The resynthesis of IκBα therefore creates a negative feedback regulation of NF-κB signaling, preventing sustained NF-κB activation and prolonged inflammatory response.In addition to the negative feedback regulation from resynthesized IκBα, the NF-κB-mediated inflammatory response is subjected to many layers of regulation, including transcriptional, translational, and posttranslational regulation (5-8). Recent studies demonstrate that selective translational control of gene expression plays an important regulatory role in the inflammatory response (7, 9). The eukaryotic translation initiation factor eIF4E has been shown to be the node of the translational control of immune response via the mTOR signaling pathway or the MAPK-Mnk1-Mnk2-eIF4E pathway (9). Upon LPS stimulation, eIF4E can be activated via its phosphorylation at S209 by Mnk1/2 (10). The phosphorylated eIF4E then activates the translation of mRNA of inflammatory genes, including IRF8 (11, 12). Interestingly, the translation of IκBα is also regulated by the phosphorylation and activation of e...

show abstract

“…The reduction in the expression of those genes after treatment with the lactobacilli suggests that all three strains probably counteract the molecular events leading to T cell activation, as shown before for the probiotic strain L. casei DN 114-001 (Carol et al 2006). Reduction of IFN-c could be a very interesting probiotic feature since, besides its crucial role for innate and adaptive immunity against intracellular pathogens, prolonged high levels of IFN-c lead to chronic autoimmune and inflammatory diseases, such as multiple sclerosis and IBD (Bouma and Strober 2003;Rovedatti et al 2009;Schoenborn and Wilson 2007). High levels of IL-17A are found in IBD; it is secreted by T h 17 cells, CD8 ?…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa

et al. 2012

View full text Add to dashboard Cite

Significant health benefits have been demonstrated for certain probiotic strains through intervention studies; however, there is a shortage of experimental evidence relative to the mechanisms of action. Here, noninvasive experimental procedure based on a colon organ culture system has been used that, in contrast to most experimental in vitro models reported, can preserve natural immunohistochemical features of the human mucosa. This system has been used to test whether commensal lactobacilli (Lactobacillus paracasei BL23, Lactobacillus plantarum 299v and L. plantarum 299v (A -)) were able to hinder inflammation-like signals induced by phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO). Whole genome microarrays have been applied to analyze expression differences, from which mRNA markers could be inferred to monitor the effect of putative probiotic strains under such conditions. Regarding the gene expression, PMA/IO treatment induced not only interleukin (IL)-2 and interferon gamma (IFN-c), as expected, but also other relevant genes related to immune response and inflammation, such as IL-17A, chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL11. The ex vivo culturing did not modify the pattern of expression of those genes or others related to inflammation. Interestingly, this study demonstrated that lactobacilli downregulated those genes and triggered a global change of the transcriptional profile that indicated a clear homeostasis restoring effect and a decrease in signals produced by activated T cells.

show abstract

Regulation of Interferon‐γ During Innate and Adaptive Immune Responses

Cited by 1,430 publications

References 281 publications

Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

Brd4 modulates the innate immune response through Mnk2–eIF4E pathway-dependent translational control of IκBα

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa

Contact Info

Product

Resources

About