ABSTRACT
Inflammatory disorders are characterized by the influx of immune cells into the vascular wall of veins and/or arteries in response to stimuli such as oxidized-LDL and various pathogens. These factors stimulate the local production of pro-inflammatory cytokines by macrophages and other cells that promote various inflammatory diseases such as atherosclerosis, Crohn’s, Alzheimer’s and diabetes. Numerous cytokines play a significant role in this process, though tumor necrosis factor (TNF) and various interleukins are thought to be among the most important regulators. These proinflammatory cytokines promote the above-described diseases by inducing endothelial cell dysfunction. In this brief commentary we will discuss some of the latest advances and discoveries in the treatment of these inflammatory diseases, making use of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) agonists.
Similar content being viewed by others
REFERENCES
Marrero MB, Bencherif M. Convergence of alpha 7 nicotinic acetylcholine receptor-activated pathways for anti-apoptosis and anti-inflammation: central role for JAK2 activation of STAT3 and NF-kappaB. Brain Res. 2009;1256:1–7.
Buccafusco JJ, Letchworth SR, Bencherif M, Lippiello PM. Long-lasting cognitive improvement with nicotinic receptor agonists: mechanisms of pharmacokinetic-pharmacodynamic discordance. Trends Pharmacol Sci. 2005;26:352–60.
Marrero MB, Lucas R, Salet C, Hauser TA, Mazurov A, Lippiello PM, et al. An alpha7 nicotinic acetylcholine receptor-selective agonist reduces weight gain and metabolic changes in a mouse model of diabetes. J Pharmacol Exp Ther. 2010;332:173–80.
Saeed RW, Varma S, Peng-Nemeroff T, Sherry B, Balakhaneh D, Huston J, et al. Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med. 2005;201:1113–23.
Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 2003;421(6921):384–8.
Shaw S, Bencherif M, Marrero MB. Janus kinase 2, an early target of alpha 7 nicotinic acetylcholine receptor-mediated neuroprotection against Abeta-(1-42) amyloid. J Biol Chem. 2002;277:44920–4.
Shaw S, Bencherif M, Marrero MB. Angiotensin II blocks nicotine-mediated neuroprotection against beta-amyloid (1-42) via activation of the tyrosine phosphatase SHP-1. J Neurosci. 2003;23:11224–8.
Takahashi HK, Liu K, Wake H, Mori S, Zhang J, Liu R, et al. Effect of nicotine on advanced glycation end product-induced immune response in human monocytes. J Pharmacol Exp Ther. 2010;332(3):1013–21.
Altavilla D, Guarini S, Bitto A, Mioni AC, Giuliani D, Bigiani A, et al. Activation of the cholinergic anti-inflammatory pathway reduces NF-kappaB activation, blunts TNF-alpha production, and protects againts splanchic artery occlusion shock. Shock. 2006;25(5):500–6.
Su X, Matthay MA, Malik AB. Requisite role of the cholinergic alpha7 nicotinic acetylcholine receptor pathway in suppressing Gram-negative sepsis-induced acute lung inflammatory injury. J Immunol. 2010;184(1):401–10.
ACKNOWLEDGMENTS
We would like to dedicate this commentary to our late colleague and friend Dr. Jerry Buccafusco, who has made seminal contributions to this field and who will be deeply missed both for his social and professional qualities.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Marrero, M.B., Bencherif, M., Lippiello, P.M. et al. Application of Alpha7 Nicotinic Acetylcholine Receptor Agonists in Inflammatory Diseases: An Overview. Pharm Res 28, 413–416 (2011). https://doi.org/10.1007/s11095-010-0283-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-010-0283-7