Additionally, it has been suggested that the cholinergic Torin 1 citations system might participate in the pathogenesis of some lung diseases since vagotomy worsened lung inflammation whereas pharmacological stimulation of ��7nAChR ameliorate lung inflammation in models of acute lung injury. However, it remains unclear whether lung inflammation is regulated by levels of VAChT. The major finding of the present study was that VAChT deficiency induces a pro-inflammatory milieu in the lung. These effects were associated with an increase in infiltration of inflammatory cells edema and increased in the number of cells expressing NF-kB and a reduction in JAK-2 levels in lung. These results suggest that long-term cholinergic deficiency affects pulmonary inflammation, pointing out the importance of acetylcholine in control pulmonary homeostasis. Known sources of ACh for the lung are the parasympathetic neurons which are dependent on VAChT to release ACh, airway epithelial cells, and immune cells, in which the dependence of VAChT was not completely understood. In airways, ACh release from parasympathetic nerves is a well-recognized bronchoconstrictor and for this reason anti-muscarinic drugs are recommended to asthmatics and COPD patients. A role for the cholinergic anti-inflammatory system has been described in models of acute systemic inflammation. The cholinergic anti-inflammatory system seems to depend on vagus nerve stimulation and on additional non-neuronal cholinergic source, such as a population of lymphocytes in the spleen. These lymphocytes release ACh that acts as an autocrine and a paracrine mediator of cytokine release from macrophages. Furthermore the stimulation of ��7nAChR ameliorates lung inflammation in a model of acute lung injury. However, it is unknown whether VAChT and endogenous ACh is involved in the maintenance of lung homeostasis. In order to evaluate the effects of cholinergic reduction in lung, we used genetically modified mice with cholinergic dysfunction. These mice were produced by targeting the VAChT gene. The release of ACh in these animals is proportional to the levels of VAChT expression and VAChT KDHOM mice have approximately 65% reduction in the levels of VAChT in the whole body. Here, we checked the VAChT mRNA expression in spinal cord and lung and confirmed this reduction, that was around 80 and 60%, respectively. These data were also confirmed by the reduction in VAChT protein content both in lung and in spinal cord. Furthermore, the absence of ACh induced a reduction in body weight and in the time of wire hang test in mutant mice. These data corroborate previously results that VAChT mice are myasthenic and had impairment in neuromuscular development and function. Inflammatory responses are characterized by both endothelial permeability alteration and inflammatory cell recruitment. We noticed both phenomena in mutant mice in which we found increased mononuclear cells, peribronchial edema around airways and increase in the amount of total protein in BALF when compared to wild-type mice. Additionally, an increase in the number of macrophages, lymphocytes, eosinophils and neutrophils was recovered in BALF of mutant mice. Although the inflammatory response was mild, is Adriamycin important to note that these animals were not submitted to any stressors to induce lung inflammation. To our knowledge, these data show for the first time that VAChT reduction induces pulmonary inflammation. We evaluated pro-inflammatory cytokines and the regulatory cytokine IL-10.