Prostaglandin E2 Stimulates AP-1-Mediated CD14 Expression in Mouse Macrophages Via Cyclic AMP-Dependent Protein Kinase A

Iwahashi, Hiroyoshi; Takeshita, Akira; Hanazawa, Shigemasa

doi:10.4049/jimmunol.164.10.5403

Cited by 30 publications

(22 citation statements)

References 43 publications

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“…41 The expression of CD14 in mouse macrophages have also been shown to be regulated by PGE 2 via cAMP-dependent PKA. 42 However, for CD14 expression PKA caused stimulation of the AP-1 transcription factor. CREB has been shown to confer a response with or without cooperating factors.…”

Section: Discussionmentioning

confidence: 99%

Induction of FcγRIIA expression in myeloid PLB cells during differentiation depends on cytosolic phospholipase A2 activity and is regulated via activation of CREB by PGE2

Hazan-Eitan

Weinstein

Hadad

et al. 2006

Blood

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FcγRIIA expressed on neutrophils and monocytes has a fundamental role in combating bacterial infections. In the present study, the requirement of cytosolic phospholipase A2 (cPLA2) for induction of FcγRIIA expression was studied in a model of cPLA2-deficient PLB-985 cells (PLB-D cells). FcγRIIA was acquired only during differentiation of PLB but not of PLB-D cells induced by either 1,25-dihydroxyvitamin D3, retinoic acid, or interferon γ. Addition of prostaglandin E2 (PGE2) to PLB-D cells undergoing differentiation restored the expression of FcγRIIA protein, whereas addition of indomethacin to PLB cells during differentiation inhibited both the production of PGE2 and the expression of FcγRIIA. Inhibition of PKA during PLB differentiation prevented FcγRIIA expression, whereas dibutyryl cAMP (dbcAMP) induced its expression in both PLB and PLB-D cells. CREB phosphorylation and CREB-CRE interaction were detected only in differentiated PLB cells and not PLB-D cells and were inhibited by indomethacin. A reporter gene containing a FcγRIIA gene promoter fragment with the CRE element was sufficient for CREB activation. Our results are the first to show that CREB activation is involved in up-regulation of FcγRIIA expression in myeloid lineages. PGE2 formed via cPLA2 activates CREB through PKA and this process is dependent on development of PGE2 receptor 4.

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Section: Discussionmentioning

confidence: 99%

Induction of FcγRIIA expression in myeloid PLB cells during differentiation depends on cytosolic phospholipase A2 activity and is regulated via activation of CREB by PGE2

Hazan-Eitan

Weinstein

Hadad

et al. 2006

Blood

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“…Although the determinants of the pro-and anti-inflammatory role of cAMP are not clearly known, it may depend on the type or the strength of the stimulus as well as the specific cellular compartments (44). In addition, this may regulate the immunomodulatory functions that are long appreciated for cAMP and its agonists (81)(82)(83). CT has been recognized as a potent immunomodulator, a property that largely depends on its ability to induce cAMP production, and has been extensively studied as a vaccine adjuvant (84).…”

Section: Discussionmentioning

confidence: 99%

cAMP Stringently Regulates Human Cathelicidin Antimicrobial Peptide Expression in the Mucosal Epithelial Cells by Activating cAMP-response Element-binding Protein, AP-1, and Inducible cAMP Early Repressor

Chakraborty

Maity

Sil

et al. 2009

Journal of Biological Chemistry

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Little is known about the regulation of the innate host defense peptide cathelicidin at the mucosal surfaces. Expression is believed to be transcriptionally regulated, and several cis-acting elements have been identified in the cathelicidin putative promoter. However, the trans-acting factors have not been clearly defined. We have recently reported that bacterial exotoxins suppress cathelicidin expression in sodium butyrate-differentiated intestinal epithelial cells (ECs), and this may be mediated through inducible cAMP early repressor. Here we have shown that cAMP-signaling pathways transcriptionally regulate cathelicidin expression in various ECs. cAMP-response elementbinding protein (CREB) and AP-1 (activator protein-1) bind to the cathelicidin putative promoter in vitro. Additionally, transcriptional complexes containing CREB, AP-1, and cathelicidin upstream regulatory sequences are formed within ECs. We have also shown that these complexes may activate cathelicidin promoter and are required for its inducible expression in ECs. This is underscored by the fact that silencing of CREB and AP-1 results in failure of ECs to up-regulate cathelicidin, and hepatitis B virus X protein may use CREB to induce cathelicidin. On the other hand, inducible cAMP early repressor competes with CREB and AP-1 for binding to the cathelicidin promoter and represses transcription, thus functioning as a counter-regulatory mechanism. Finally, both CREB and AP-1 were shown to play major roles in the regulation of cathelicidin in sodium butyrate-differentiated HT-29 cells. This is the first report of a detailed mechanistic study of inducible cathelicidin expression in the mucosal ECs. At the same time, it describes a novel immunomodulatory function of cAMP.

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“…The concentration of DMSO used was the same as the concentration in the vehicle control. For all inhibitors, a dose response was observed in relation to ERK 1/2 phosphorylation, and the concentrations used in subsequent studies were chosen based on the dose response and the results of previous studies with macrophages (10,17,24,33). None of the inhibitors used had a significant effect on the uptake of the mycobacteria by the macrophages.…”

Section: Methodsmentioning

confidence: 99%

Differential Activation of the Transcription Factor Cyclic AMP Response Element Binding Protein (CREB) in Macrophages following Infection with Pathogenic and Nonpathogenic Mycobacteria and Role for CREB in Tumor Necrosis Factor Alpha Production

2005

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Previous studies in our laboratory have shown a differential activation of the mitogen-activated protein kinases (MAPKs) in primary bone marrow-derived macrophages following infection with pathogenic Mycobacterium avium compared to the activation following infection with nonpathogenic Mycobacterium smegmatis. Additionally, M. smegmatis-infected macrophages produced significantly elevated levels of tumor necrosis factor alpha (TNF-␣) compared to the levels produced by M. avium-infected macrophages. The TNF-␣ production was dependent on both p38 and extracellular signal-regulated kinase 1/2 (ERK 1/2) activation. However, the macrophage transcription factors downstream of the MAPKs, which were required for TNF-␣ production, remained undefined. In this study we determined that the transcription factor cyclic AMP response element binding protein (CREB) is significantly more activated in M. smegmatis-infected macrophages than in M. avium-infected macrophages. We also found that CREB activation was dependent on p38 and protein kinase A but not on ERK 1/2 or calmodulin kinase II. Moreover, mutating the cAMP-responsive element on the TNF-␣ promoter resulted in significantly diminished promoter activity following M. smegmatis infection but not M. avium infection. The inability of macrophages infected with M. avium to sustain MAPK activation and to produce high levels of TNF-␣ was due, in part, to an increase in serine/threonine phosphatase PP2A activity. Our studies are the first to demonstrate an important role for the transcription factor CREB in TNF-␣ production by mycobacterium-infected macrophages, as well as a role for M. avium's induction of PP2A phosphatase activity as a mechanism to limit macrophage activation.Mycobacterium avium is an opportunistic pathogen that affects people with suppressed immune systems, particularly people with late-stage human immunodeficiency virus or chronic lung diseases. In AIDS patients, M. avium is commonly disseminated and can involve almost any internal organ, especially the liver, spleen, and bone marrow. Moreover, M. avium is responsible for increased morbidity and mortality in human immunodeficiency virus-infected individuals (6).M. avium is a facultative intracellular pathogen that resides within the phagosome of the host macrophage. The macrophage is the first line of defense against invading microorganisms, and it functions to phagocytose and subsequently destroy these invaders within a phagolysosome. However, following phagocytosis, M. avium, like other species in the genus Mycobacterium, including Mycobacterium tuberculosis and Mycobacterium leprae, has been shown to halt the maturation of the phagosome through coordinated blocking of lysosome fusion with the phagosome. Thus, the M. avium-containing phagosome fails to acquire lysosomal lytic enzymes, nor does it acidify, due to a scarcity of the proton ATPases (25). However, macrophages have another inherent defense mechanism against mycobacterial diseases. Macrophages are stimulated to secrete a large panel of inflammatory...

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Prostaglandin E2 Stimulates AP-1-Mediated CD14 Expression in Mouse Macrophages Via Cyclic AMP-Dependent Protein Kinase A

Cited by 30 publications

References 43 publications

Induction of FcγRIIA expression in myeloid PLB cells during differentiation depends on cytosolic phospholipase A2 activity and is regulated via activation of CREB by PGE2

Induction of FcγRIIA expression in myeloid PLB cells during differentiation depends on cytosolic phospholipase A2 activity and is regulated via activation of CREB by PGE2

cAMP Stringently Regulates Human Cathelicidin Antimicrobial Peptide Expression in the Mucosal Epithelial Cells by Activating cAMP-response Element-binding Protein, AP-1, and Inducible cAMP Early Repressor

Differential Activation of the Transcription Factor Cyclic AMP Response Element Binding Protein (CREB) in Macrophages following Infection with Pathogenic and Nonpathogenic Mycobacteria and Role for CREB in Tumor Necrosis Factor Alpha Production

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