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The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.

ABSTRACT: Immune-mediated inflammatory diseases (IMIDs) encompass a wide range of seemingly unrelated conditions, such as multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel diseases, asthma, chronic obstructive pulmonary disease, and systemic lupus erythematosus. Despite differing etiologies, these diseases share common inflammatory pathways, which lead to damage in primary target organs and frequently to a plethora of systemic effects as well. The purinergic signaling complex comprising extracellular nucleotides and nucleosides and their receptors, the P2 and P1 purinergic receptors, respectively, as well as catabolic enzymes and nucleoside transporters is a major regulatory system in the body. The purinergic signaling complex can regulate the development and course of IMIDs. Here we provide a comprehensive review on the role of purinergic signaling in controlling immunity, inflammation, and organ function in IMIDs. In addition, we discuss the possible therapeutic applications of drugs acting on purinergic pathways, which have been entering clinical development, to manage patients suffering from IMIDs.

SUBMITTER: Antonioli L

PROVIDER: S-EPMC6592405 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.

Antonioli Luca L Blandizzi Corrado C Pacher Pál P Haskó György G

Pharmacological reviews 20190701 3

Immune-mediated inflammatory diseases (IMIDs) encompass a wide range of seemingly unrelated conditions, such as multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel diseases, asthma, chronic obstructive pulmonary disease, and systemic lupus erythematosus. Despite differing etiologies, these diseases share common inflammatory pathways, which lead to damage in primary target organs and frequently to a plethora of systemic effects as well. The purinergic signaling complex compris ...[more]

PMID: 31235653

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Project description:Background:Mononuclear phagocytes, such as monocytes, macrophages, and dendritic cells, are important cellular components of the innate immune system that contribute to the pathogenesis of many intestinal inflammatory diseases. Summary:While mononuclear phagocytes play a key role in the induction of inflammation in many different tissues through production of pro-inflammatory cytokines and chemokines (such as IL-1, TNF, IL-6, IL-8 and MCP-1), free oxygen radicals (also termed 'oxidative burst'), proteases (such as cathepsins) and tissue-degrading enzymes (such as metalloproteinases), resident macrophages as well as dendritic cells in the intestine display an anergic and 'tolerogenic' phenotype mediating tolerance to commensal bacteria. In recent years many single nucleotide polymorphisms (SNPs) in genes mainly expressed in the above-mentioned cell types have been identified to convey an increased risk of autoimmune diseases. SNPs in the NOD2, ATG16L1 and TNFSF15 genes, which are involved in the function of the innate immune cells, are identified as risk factors for Crohn's disease (CD). Of note, these genes are involved in the different functions in the innate immune cells. For example, while NOD2 is required for intracellular recognition of microbial components, ATG16L1 is involved in autophagy responses against intracellular microbes. Likewise, TNFSF15 contributes to the induction of inflammatory responses by innate immune cells. Furthermore, the frequency of mutations in these genes differs by ethnicity. Genetic variations in the NOD2 and ATG16L1 genes are associated with CD in Caucasians but much less in Eastern Asian populations, whereas SNPs in TNFSF15 are dominated in Asian populations. Thus, different genetic risks may eventually lead to similar impairments in innate immune cells, thereby developing the same disease in Western and Asian patients with CD. Key Messages:Despite differences in risk genes, similar mechanisms associated with the innate immune system may trigger autoimmune and chronic inflammatory intestinal diseases in East and West.

Dataset Information

The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.

Publications

The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.

Similar Datasets

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