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Smoking is the leading preventable cause of death worldwide and tobacco addiction has become a serious public health problem. Nicotine is the main addictive component of tobacco, and the majority of people that smoke regularly develop nicotine dependence. Nicotine addiction is deemed to be a chronic mental disorder. Although it is well known that nicotine binds to the nicotinic acetylcholine receptors (nAChRs) and activates the mesolimbic dopaminergic system (MDS) to generate the pleasant and rewarding effects, the molecular mechanisms of nicotine addiction are not fully understood. Brain-derived neurotrophic factor (BDNF) is the most prevalent growth factor in the brain, which regulates neuron survival, differentiation, and synaptic plasticity, mainly through binding to the high affinity receptor tyrosine kinase receptor B (TrkB). BDNFgene polymorphisms are associated with nicotine dependence and blood BDNF levels are altered in smokers. In this review, we discussed the effects of nicotine on BDNF expression in the brain and summarized the underlying signaling pathways, which further indicated BDNF as a key regulator in nicotine dependence. Further studies that aim to understand the neurobiological mechanism of BDNF in nicotine addcition would provide a valuable reference for quitting smoking and developing the treatment of other addictive substances.

Interleukin-37 (IL-37) was discovered as a new member of pro-inflammatory IL-1 superfamily. However, further studies suggested that IL-37 plays a critical anti-inflammatory role in innate and adaptive immunity. IL-37 may suppress the inflammatory process via intracellular SMAD family member 3 (SMAD3) and extracellular IL-18 Receptor alpha (IL-18Rα) signaling pathway, respectively. Meanwhile, the abnormal expression of IL-37 was observed in immune-mediated inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, atherosclerosis, systemic lupus erythematosus, asthma, and multiple sclerosis, which suggest IL-37 is a potential therapeutic target for these diseases. In this review, we summarize the anti-inflammatory mechanism of IL-37 and discuss the critical roles of IL-37 in the pathogenesis of these diseases. Further studies are required to confirm the effectiveness of IL-37 as a novel target for these inflammatory diseases.

Background: Human Interleukin 37 (IL37), a unique anti-inflammatory cytokine of IL1 family member, plays critical roles in innate and adaptive immunity and inflammation. Objective: Preparation of high purity and tag-removed recombinant IL37 protein (rIL37) is critical for its clinical application. Method: In this study, we constructed an N-terminal cleavable GST-fused IL37 expression vector for recombinant expression. Results: Subsequent to transformation and optimization of the induction temperature, the soluble expression level of rIL37 was 306.5 mg/L of culture medium at 18 °C induction in Escherichia coli. Meanwhile, rIL37 was digested on beads by GST-HRV3C protease during GST affinity chromatography. After further purification, the purity of rIL37 was higher than 99 %. Finally, the antiinflammatory activity of tag-removed protein was verified by the results showing that rIL37 suppressed IL1β production in PBMCs. Conclusion: This work presents a protocol to produce high purity and tag-removed rIL37 with antiinflammatory activity, which provides the firm basis for advancing clinical application in human IL37-related inflammatory diseases.