The role of the cholinergic anti-inflammatory pathway in autoimmune rheumatic diseases.

The cholinergic anti-inflammatory pathway (CAP) is a classic neuroimmune pathway, consisting of the vagus nerve, acetylcholine (ACh)-the pivotal neurotransmitter of the vagus nerve-and its receptors. This pathway can activate and regulate the activities of immune cells, inhibit cell proliferation and differentiation, as well as suppress cytokine release, thereby playing an anti-inflammatory role, and widely involved in the occurrence and development of various diseases; recent studies have demonstrated that the CAP may be a new target for the treatment of autoimmune rheumatic diseases. In this review, we will summarize the latest progress with the view of figuring out the role of the cholinergic pathway and how it interacts with inflammatory reactions in several autoimmune rheumatic diseases, and many advances are results from a wide range of experiments performed in vitro and in vivo.

Structurally diverse steroids from an endophyte of Aspergillus tennesseensis 1022LEF attenuates LPS-induced inflammatory response through the cholinergic anti-inflammatory pathway.

The emerging cholinergic anti-inflammatory pathway plays a key role in regulating inflammation. Steroids are known to possess remarkable anti-inflammatory activity. However, the links between steroids and the cholinergic anti-inflammatory pathway remain unidentified. In this study, eight steroids (1-8) featuring five different structural types were characterized from an endophytic fungus Aspergillus tennesseensis 1022LEF, and were subsequently evaluated for their potential role in regulating the cholinergic anti-inflammatory pathway. As a result, compound 8, with the best potency, showed remarkable anti-inflammatory activity at the nanomolar to low micromolar level. Further pharmacological study indicated that 8 notably increased α7nAchR expression and inhibited the activation of its down-stream signaling pathways. Collectively, the present study not only highlighted the potential correlation between steroids and the cholinergic anti-inflammatory pathway, but also identified 8 as a dual-functional modulator via directly inhibition to acetylcholinesterase as well as up-regulation of α7nAchR expression.

The cholinergic anti-inflammatory pathway: An innovative treatment strategy for neurological diseases.

Acetylcholine (ACh), as a classical neurotransmitter, regulates the neuronal network in response to internal and external stimuli. In recent decades, the biology of ACh has been endowed with unparalleled new insights, especially with respect to cholinergic anti-inflammatory properties in non-neuronal cells. In fact, a mechanism frequently referred to as the "cholinergic anti-inflammatory pathway" has been termed to describe interactions between the central nervous system (CNS) and the immune system via vagus nerve. As well documented, immune cells express choline acetyltransferase, a direct synthetase for ACh, and other corresponding cholinergic components. Alternatively, the ACh released from immune cells or cholinergic neurons modulates immune function in an autocrine/paracrine manner by acting on its receptors. Moreover, muscarinic or nicotinic ACh receptors on various immune cells and CNS glial cells administer the work of their respective agonists, causing functional and biochemical changes. In this review, we focus on the anti-inflammatory benefits of non-neuronal and neuronal ACh as a means of providing new insights into treating inflammation-related neurological diseases, as exemplified by those described herein.