Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-activating Polypeptide Inhibit Interleukin-12 Transcription by Regulating Nuclear Factor κB and Ets Activation

Delgado, Mario; Ganea, Doina

doi:10.1074/jbc.274.45.31930

Cited by 100 publications

(84 citation statements)

References 71 publications

(82 reference statements)

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“…These results differ from results obtained with the macrophages cell line Raw 264.7. Mario and his colleagues showed an inhibitory effect of PACAP or LPS-induced NF-κB binding to IL-12 p40 promoter in Raw 264.7 [13], [15]. These differences may be due to different experimental systems.…”

Section: Discussionmentioning

confidence: 99%

“…Although these subunits share regions of homology, they also have unique structural features and their gene expression regulation is distinct. IL-12 p35 subunit is synthesized in many cells and tissues, while p40 synthesis is largely restricted to activated mononuclear phagocytes and dendritic cells [14], [15]. As a result, IL-12 p40 subunit expression is often considered to be the limiting factor for IL-12 expression.…”

Section: Introductionmentioning

confidence: 99%

“…However there is little information about the mechanism for cAMP-signal-inhibitory effect on LPS-induced IL-12 expression in macrophages. There is a single report on this subject in macrophage cell line [15]. The mechanism in murine or human macrophages is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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cAMP elevators inhibit LPS-induced IL-12 p40 expression by interfering with phosphorylation of p38 MAPK in Murine Peritoneal Macrophages

et al. 2002

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mediated signaling may play a suppressive role in immune response. We previously found that the cAMPelevators (CTx and 8-Br-cAMP) inhibited IL-12, IL-1a, IL-6 gene expression, but increased the transcriptional levels of IL-10 and IL-1Ra in LPS-treated murine peritoneal macrophages. The present study examined a possible molecular mechanism involved in cAMP elevators-induced inhibition of IL-12 p40 expression in response to LPS. Our data demonstrated that cAMP elevators downregulated IL-12 p40 mRNA expression and IL-12 p70 production in murine peritoneal macrophages. Subsequent studies revealed that cAMP-elevators blocked phosphorylation of p38 MAPK, but did not affect the activity of NF-B binding to . This is the first report that cAMP elevators inhibit LPS-induced IL-12 production by a mechanism that is associated, at least in part, with p38-dependent inhibition by cAMP signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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cAMP elevators inhibit LPS-induced IL-12 p40 expression by interfering with phosphorylation of p38 MAPK in Murine Peritoneal Macrophages

et al. 2002

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“…NIH-PA Author Manuscript NIH-PA Author Manuscript costimulatory factors (Figure 2), including nuclear factor-κB (NFκB), mitogen-activated protein kinases (MAPK), interferon regulatory factor 1 (IRF1) and activator protein 1 (AP1) [18,19,[21][22][23][24]33,34,37].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…Several cAMP-inducing agents have been shown to be potent anti-inflammatory factors [3,8,64]. VIP downregulates the activity of several transduction pathways and their associated transcription factors essential for the transcriptional activation of most inflammatory cytokines, chemokines and costimulatory factors (Figure 2), including nuclear factor-κB (NFκB), mitogen-activated protein kinases (MAPK), interferon regulatory factor 1 (IRF1) and activator protein 1 (AP1) [18,19,[21][22][23][24]33,34,37].…”

Section: Vip Acts As An Anti-inflammatory Agent In Innate Immunitymentioning

confidence: 99%

Tuning immune tolerance with vasoactive intestinal peptide: A new therapeutic approach for immune disorders

et al. 2007

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The induction of immune tolerance is essential for the maintenance of immune homeostasis and to limit the occurrence of exacerbated inflammatory and autoimmune conditions. Multiple mechanisms act together to ensure self-tolerance, including central clonal deletion, cytokine deviation and induction of regulatory T cells. Identifying the factors that regulate these processes is crucial for the development of new therapies of autoimmune diseases and transplantation. The vasoactive intestinal peptide (VIP) is a well-characterized endogenous anti-inflammatory neuropeptide with therapeutic potential for a variety of immune disorders. Here we examine the latest research findings, which indicate that VIP participates in maintaining immune tolerance in two distinct ways: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T-cell effectors. KeywordsInflammation; Autoimmunity; Regulatory T cells; Tolerance; Neuroimmunology; Neuropeptide Immune tolerance versus autoimmunityProtection against infection is fundamental to the survival of all complex organisms. The successful elimination of most pathogens requires crosstalk between the innate and adaptive arms of the immune system. The innate immune system recognizes pathogen-associated molecular signatures through pattern-recognition receptors, such as Toll-like receptors (TLRs), which induce the release of pro-inflammatory cytokines, chemokines and free radicals, the recruitment of inflammatory cells to the site of infection, and the lysis of infected host cells by natural killer cells and cytotoxic T lymphocytes. Although critical for the successful elimination of pathogens, the inflammatory process needs to be limited, since an excessive response can result in severe inflammation and collateral tissue damage. Inflammatory responses also increase the risk of inducing harmful autoimmune responses, where immune cells and the molecules that respond to pathogen-derived antigens also react to self-antigens. *Corresponding Author: Mario Delgado, Instituto de Parasitologia y Biomedicina, CSIC, Avd. Conocimiento, PT Ciencias de la Salud, Granada 18100, Spain. Phone: 34-958-181665. Fax: 34-958-181632. email: mdelgado@ipb.csic.es Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptPeptides. Author manuscript; available in PMC 2008 September 1. Published in final edited form as:Peptides. 2007 September ; 28(9): 1833-1846. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Aut...

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Anti-inflammatory properties of the type 1 and type 2 vasoactive intestinal peptide receptors: role in lethal endotoxic shock

et al. 2000

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Vasoactive intestinal peptide (VIP) is a neuropeptide that can modulate several immune aspects. Previous reports showed that VIP attenuates the deleterious consequences of septic shock by inhibiting the production of pro‐inflammatory agents and stimulating the production of anti‐inflammatory cytokines in activated macrophages. In this study, by using selective VIP agonists, we investigated the differential involvement of the VIP receptors in the anti‐inflammatory role of VIP. Both the type 1 VIP receptor (VPAC1) agonist, [K15, R16, L27] VIP 1–7‐GRF 8–27, and the type 2 VIP receptor (VPAC2) agonist, Ro25–1553, protected mice from lethal endotoxemia by inhibiting the macrophage‐derived pro‐inflammatory mediators IL‐6, TNF‐α, IL‐12 and NO, and by stimulating the production of the anti‐inflammatory cytokine IL‐10. In addition, both VIP and VPAC1 agonist, but not the VPAC2 agonist, reduced in vitro and in vivo the expression of the co‐stimulatory B7.1/B7.2 molecules, and the subsequent stimulatory activity for T helper cells in stimulated macrophages. The higher effectiveness of the VPAC1 agonist compared with the VPAC2 agonist suggests that VPAC1 is the major mediator of the anti‐inflammatory action of VIP. Since VIP and the two agonists appear to affect multiple cytokines and inflammatory factors, they might provide a more efficient therapeutical alternative to the use of specific cytokine antibodies or antagonists.

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Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-activating Polypeptide Inhibit Interleukin-12 Transcription by Regulating Nuclear Factor κB and Ets Activation

Cited by 100 publications

References 71 publications

cAMP elevators inhibit LPS-induced IL-12 p40 expression by interfering with phosphorylation of p38 MAPK in Murine Peritoneal Macrophages

cAMP elevators inhibit LPS-induced IL-12 p40 expression by interfering with phosphorylation of p38 MAPK in Murine Peritoneal Macrophages

Tuning immune tolerance with vasoactive intestinal peptide: A new therapeutic approach for immune disorders

Anti-inflammatory properties of the type 1 and type 2 vasoactive intestinal peptide receptors: role in lethal endotoxic shock

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