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The Yin and Yang of Non-Neuronal α7-Nicotinic Receptors in Inflammation and Autoimmunity

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The alkaloid nicotine, a major addictive component of tobacco, exerts anti-inflammatory and immunemodulating activities on multiple cell types, such as T cells, B cells, dendritic cells, mononuclear phagocytes and polymorphonuclear leukocytes, in lung, spleen, liver, kidney and gastrointestinal tract. In addition, nicotine may blunt pro-inflammatory cytokine release, with prominent effects on T helper type 1 (Th1) and Th17 cytokines. The nonneuronal α7-nicotinic cholinergic receptors are a primary target for nicotine through the JAK2 and STAT3/NF-κB pathways, ultimately mediating the inhibition of pro-inflammatory gene transcription. The present paper reviews the growing evidence in favor of detrimental as well as beneficial effects of nicotine and other α7-nicotininc receptor agonists in pre-clinical models of organ-specific and systemic inflammatory and autoimmune diseases. These data may portend favorable implications for the targeted treatment of chronic and debilitating human disorders, such as diabetes, arthritis, asthma and inflammatory bowel disease, with α7-selective ligands.





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Keywords: Nicotinic Receptors; allergic asthma; anti-inflammatory; arthritis; autoimmune encephalomyelitis; cholinergic; cytokines; diabetes; immunity; inflammation

Document Type: Research Article

Affiliations: Department of Pediatric Hematology/Oncology, IRCCS Bambino Gesù Children’s Hospital, Piazza Sant’Onofrio 4, 00165 Rome, Italy.

Publication date: May 1, 2012

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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