PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease

Banner, Katharine H.; Trevethick, Michael A.

doi:10.1016/j.tips.2004.06.008

Cited by 82 publications

(61 citation statements)

References 51 publications

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“…Recently, it was shown that the modulation of cAMP by PDE type 4 inhibitors can be effective in reducing inflammation by reducing cytokine release in a variety of cell types, and these drugs are being tested in chronic obstructive pulmonary disease and bowel disease (12)(13)(14). However, most PDE type 4 inhibitors can produce nausea and vomiting, and active research for more tolerable agents is ongoing (12).…”

Section: Vinpocetine Reduces Inflammation By Ikk Inhibitionmentioning

confidence: 99%

Vinpocetine as a potent antiinflammatory agent

Medina

2010

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

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Section: Vinpocetine Reduces Inflammation By Ikk Inhibitionmentioning

confidence: 99%

Vinpocetine as a potent antiinflammatory agent

Medina

2010

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

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“…A PDE4 faz parte da superfamília de enzimas fosfodiesterase (PDE) e está amplamente distribuída em tecidos de mamíferos possuindo papel fundamental na sinalização celular através da hidrólise de AMPc e GMPc, regulando várias funções celulares. A família PDE4 é expressa particularmente em tipos de células infl amatórias, do sistema imune e em células da musculatura lisa brônquica (Banner & Trevethick, 2004;Barnes, 2004;Lugnier, 2006 inibidores de PDE4 possuem atividade tanto em células infl amatórias e da musculatura do brônquio (Leath et al, 2005;Lazaar & Panettieri, 2004).…”

Section: Cromonasunclassified

“…Alguns fármacos, como cilomilast (Arifl o®) e rofl umilast (Daxas®), já foram amplamente estudados em ensaios clínicos e mostraram potencial inibitório na fase tardia da asma, diminuindo, conseqüentemente, a resposta alérgica. Entretanto, estes fármacos, como a maioria dos inibidores da PDE4, possuem efeitos colaterais inaceitáveis, em particular náuseas e vômitos, um dos motivos que levaram à limitação do uso de xantinas (Banner & Trevethick, 2004;Barnes, 2004;Lugnier, 2006).…”

Section: Inibidores Da Fosfodiesterase 4 (Pde4)unclassified

Substâncias de origem vegetal potencialmente úteis na terapia da asma

Corrêa¹,

Melo²,

Costa³

2008

Rev. bras. farmacogn.

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RESUMO:A asma é uma doença infl amatória crônica, que representa um problema de saúde pública com altos números de óbitos e elevado impacto socioeconômico. A patologia é caracterizada pela fase imediata, mediada pela resposta aguda de células infl amatórias, e a tardia, que é responsável pela resposta com envolvimento de células específi cas do sistema imunológico. Atualmente, os principais tipos de fármacos utilizados no tratamento da asma são os broncodilatadores e agentes antiinfl amatórios, que aliviam os sintomas de broncoespasmo e diminuem a infl amação das vias aéreas. Entretanto, terapias com esses medicamentos não são totalmente efi cazes e provocam efeitos adversos. A escassez de fármacos seguros e o baixo acesso da população carente aos tratamentos utilizados estimulam a busca de novas substâncias potencialmente úteis no tratamento da asma. Produtos naturais de origem vegetal representam um grande potencial farmacológico contra asma, uma vez que podem fornecer moléculas diversas com mecanismos específi cos para tratamento e controle da patologia. A busca por terapias mais efi cientes e específi cas para o processo asmático mostra que a procura nos produtos naturais é promissora e possui um papel importante para a descoberta de novas terapias contra a asma.Unitermos: Asma, infl amação crônica, células Th2, plantas medicinais, produtos naturais, metabólitos secundários.ABSTRACT: "Natural products from plant origin potentially usefull in the asthma therapy". Asthma is a chronic infl ammatory disease, which represents a huge public health problem in developed and developing countries, has high death rates and elevated socioeconomic implications. The pathology is characterized by two different phases: the initial stage, mediated by acute infl ammatory cell response and the late phase, responsible for specifi c immune cells. Currently, the main drugs used for asthma treatment are bronchodilator and anti-infl ammatory agents, which mechanisms focus the relief of symptoms and attenuation of airway infl ammation. However, therapies with those drugs have side effects besides they are not totally effective. Poor accessibility in the development countries and scarcity of safety drugs lead the search for new drugs to asthma treatment. Herbal natural products have elevated pharmacological potential against asthma, once they provide several molecules with specifi c mechanisms for the pathology control and treatment. Thus, search in herbal natural products plays an important role to fi nd out specifi c and effective mechanisms.

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“…Secondly, VIP exerts its biological actions through various G-protein-coupled receptors (VPAC1, VPAC2 and PAC1), that are expressed in several immune cells, including T cells, macrophages, monocytes, dendritic cells (DCs) and neutrophils [36]. Finally, VIP signaling involves the activation of cAMP/protein kinase A (PKA) pathway [36], which is considered an immunosuppressive signal [3].…”

Section: Vip a Well-known Anti-inflammatory Factormentioning

confidence: 99%

“…The answer may lie in the fact that VIP exerts most of its effects, in the majority of tissues, via the cAMP/PKA pathway, including the downregulation of inflammatory mediators [12,18,25,33,[35][36][37]66]. 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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PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease

Cited by 82 publications

References 51 publications

Vinpocetine as a potent antiinflammatory agent

Vinpocetine as a potent antiinflammatory agent

Substâncias de origem vegetal potencialmente úteis na terapia da asma

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

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