Cyclic AMP Response Element-Binding Protein Positively Regulates Production of IFN-γ by T Cells in Response to a Microbial Pathogen

Samten, Buka; Howard, Susan T.; Weis, Steven E.; Wu, Shijie; Shams, Homayoun; Townsend, John C.; Safi, Hassan; Barnes, Peter F.

doi:10.4049/jimmunol.174.10.6357

Cited by 36 publications

(41 citation statements)

References 31 publications

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“…We have shown previously that the transcription factors cyclic AMP response element binding protein (CREB), activating transcription factor w (ATF-2), and c-Jun bind to the IFN-␥ proximal promoter and upregulate IFN-␥ production by T cells (37,38). The phosphorylation of these transcription factors increases their binding to the transcriptional complex.…”

Section: Resultsmentioning

confidence: 99%

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Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis

et al. 2011

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Smoking is associated with increased susceptibility to tuberculosis and influenza. However, little information is available on the mechanisms underlying this increased susceptibility. Mice were left unexposed or were exposed to cigarette smoke and then infected with Mycobacterium tuberculosis by aerosol or influenza A by intranasal infection. Some mice were given a DNA vaccine encoding an immunogenic M. tuberculosis protein.Gamma interferon (IFN-␥) production by T cells from the lungs and spleens was measured. Cigarette smoke exposure inhibited the lung T-cell production of IFN-␥ during stimulation in vitro with anti-CD3, after vaccination with a construct expressing an immunogenic mycobacterial protein, and during infection with M. tuberculosis and influenza A virus in vivo. Reduced IFN-␥ production was mediated through the decreased phosphorylation of transcription factors that positively regulate IFN-␥ expression. Cigarette smoke exposure increased the bacterial burden in mice infected with M. tuberculosis and increased weight loss and mortality in mice infected with influenza virus. This study provides the first demonstration that cigarette smoke exposure directly inhibits the pulmonary T-cell response to M. tuberculosis and influenza virus in a physiologically relevant animal model, increasing susceptibility to both pathogens.

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Section: Resultsmentioning

confidence: 99%

“…Whole-cell protein extracts of T cells from lungs and spleens were prepared as described previously (36)(37)(38) and were quantified by bicinchoninic acid assay (Pierce Biotechnology). SDS-PAGE and Western blotting were performed as previously described (36).…”

Section: Methodsmentioning

confidence: 99%

Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis

et al. 2011

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“…The lungs were then excised and homogenized in 2.0 ml of lysis buffer. Lysates were processed through three freeze and thaw cycles as described previously (34), and insoluble material was removed by centrifugation at 15,000 ϫ g. Protein was quantified using the BCA assay. Expression of SP-R210 was assessed by Western blot analysis using affinitypurified anti-Myo18A (Protein Tech) antibodies.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were then washed once in 50 mM Tris, pH 8.0, and once in PBS. Labeled cells were detached in a cell stripper and washed, and cell extracts were generated in lysis buffer (containing 1% Nonidet P-40, 50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 1 mM PMSF, 2 g/ml leupeptin, 2 g/ml aprotinin, 10 g/ml chymostatin, and 10 g/ml trypsin-chymotrypsin) by repeated freeze and thaw cycles as described previously (27,34). Cell lysates were then incubated for 1 h on a rotator at 4°C with 100 l of a 50% suspension of streptavidin-agarose.…”

Section: Methodsmentioning

confidence: 99%

Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

Sever-Chroneos

Krupa

Davis

et al. 2011

Journal of Biological Chemistry

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There is limited knowledge about host factors that facilitate eradication of Staphylococcus aureus infection in the lung. Methicillin-resistant S. aureus has remained a major cause of hospital-and health care-associated pneumonia since its appearance over 40 years ago and has recently become a more prominent etiology in community acquired pneumonia. Colonization of nasal epithelium with S. aureus, a normal occurrence in over 20% of the population, increases the risk for the development of staphylococcal pneumonia (1). Furthermore, S. aureus co-infections are a major complication contributing to high morbidity and mortality during both pandemic and seasonal influenza virus pneumonia (2). S. aureus deploys a combination of virulence factors, including adhesins, toxins, and immunomodulatory molecules, that facilitate infection of different host tissues (3, 4).Surfactant protein A (SP-A) 3 is a crucial component of the pulmonary innate immune system in the alveolar spaces (5, 6). SP-A is the major protein constituent of pulmonary surfactant; it is involved in organization of large aggregate surfactant phospholipids lining the alveolar surface and acts as an opsonin for pathogens (7). SP-A is incorporated in the tubular myelin fraction of pulmonary surfactant that covers the alveolar lining fluid of the distal airway epithelium. The presence of pathogen-derived molecules may trigger reorganization of surfactant lipids (8 -11) and exposure of SP-A to bind pathogens at points of entry on the surfactant interface. Alveolar macrophages in the aqueous hypophase may then patrol areas of disturbance on the surfactant layer binding SP-A-opsonized bacteria. SP-A binds pathogens via a carboxyl-terminal carbohydrate recognition domain in a calcium-dependent manner. Amino-terminal collagen-like and coiled-coil do-

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“…32 CREB proteins are essential regulators for T-cell function and cytokine production (e.g., of IFNg). 33,34 Moreover, PGE2-induced cAMP was described to also activate the raft-associated enzyme c-src tyrosine kinase (CSK), which negatively regulates the phosphorylating activities of the TCR signaling kinase LCK, the Z chain TCR associated kinase ZAP-70 and AKT in T cells. 35,36 Although EP2 and EP4 receptors share the same signaling pathway, a distinguishing feature of the EP4 receptor is its activation of the PI3K signaling pathway resulting in subsequent nuclear factor kB (NF-kB) activation and thus TNFa release.…”

Section: E988460-6mentioning

confidence: 99%

Resistance of cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells against γδ T cell cytotoxicity

Gonnermann

Oberg

Kellner³

et al. 2015

OncoImmunology

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Keywords: Cox-2, cytotoxicity, gammadelta T lymphocytes, human, pancreatic ductal adenocarcinoma, PGE2Abbreviations: BrHPP, bromohydrin-pyrophosphate; Cox, cyclooxygenase; n-BP, nitrogen-containing bisphosphonates; PAg, phosphorylated antigen; PDAC, pancreatic ductal adenocarcinoma; PG, prostaglandins; RTCA, Real Time Cell Analyzer; TCR, T cell receptor.The prostaglandin (PG) synthetase cyclooxygenase 2 (Cox-2) promotes tumorigenesis, tumor progression, and metastasis in a variety of human cancer entities including pancreatic ductal adenocarcinoma (PDAC). In this study, we demonstrate that in PDAC cells such as Colo357 cells, enhanced Cox-2 expression and increased release of the Cox-2 metabolite prostaglandin E2 (PGE2) promotes resistance against gd T cell-mediated lysis. Co-culture with activated gd T cells induced an upregulation of Cox-2 expression in Colo357 cells, and thereby an enhanced PGE2 release, in response to tumor necrosis factor a .TNFa/ secretion from gd T cells. The PGE2-mediated inhibition of gd T cell cytotoxicity against Cox-2-expressing PDAC cells can be partially overcome by Cox-2 inhibitors. Our results show that differences between PDAC cells in regards to sensitivity to gd T-cell cytotoxicity can be due to distinct levels of Cox-2 expression associated with varying amounts of PGE2 release. While gd T cell cytotoxicity against PDAC cells expressing low levels of Cox-2 can be effectively enhanced by tribody [(Her2) 2 £Vg9] with specificity for Vg9 T cell receptor and HER-2/neu on PDAC cells, a combination of tribody [(Her2) 2 £Vg9] and Cox-2 inhibitor is necessary to induce complete lysis of Cox-2 high expressing Colo357. In conclusion, our results suggest that the application of tribody [(Her2) 2 £Vg9] that enhances gd T-cell cytotoxicity and Cox-2 inhibitors that overcome PGE2-mediated resistance of PDAC cells to the cytotoxic activity of gd T cells might offer a promising combined immunotherapy for pancreatic cancer.

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Cyclic AMP Response Element-Binding Protein Positively Regulates Production of IFN-γ by T Cells in Response to a Microbial Pathogen

Cited by 36 publications

References 31 publications

Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis

Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis

Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

Resistance of cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells against γδ T cell cytotoxicity

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