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Acute lung injury induced by intestinal ischemia/reperfusion (I/R) is a relevant clinical condition. Acetylcholine (ACh) and the α7 nicotinic ACh receptor (nAChRα-7) are involved in the control of inflammation. Mice with reduced levels of the vesicular ACh transporter (VAChT), a protein responsible for controlling ACh release, were used to test the involvement of cholinergic signaling in lung inflammation due to intestinal I/R. Female mice with reduced levels of VAChT (VAChT-KD HOM ) or wild-type littermate controls (WT) were submitted to intestinal I/R followed by 2 h of reperfusion. Mortality, vascular permeability, and recruitment of inflammatory cells into the lung were investigated. Parts of mice were submitted to ovariectomy (OVx) to study the effect of sex hormones or treated with PNU-282,987 (nAChRα-7 agonist). A total of 43.4% of VAChT-KD HOM -I/R mice died in the reperfusion period compared to 5.2% of WT I/R mice. The I/R increased lung inflammation in both genotypes. In VAChT-KD HOM mice, I/R increased vascular permeability and decreased the release of cytokines in the lung compared to WT I/R mice. Ovariectomy reduced lung inflammation and permeability compared to non-OVx, but it did not avoid mortality in VAChT-KD HOM -I/R mice. PNU treatment reduced lung permeability, increased the release of proinflammatory cytokines and the myeloperoxidase activity in the lungs, and prevented the increased mortality observed in VAChT-KD HOM mice. Cholinergic signaling is an important component of the lung protector response against intestinal I/R injury. Decreased cholinergic signaling seems to increase pulmonary edema and dysfunctional cytokine release that increased mortality, which can be prevented by increasing activation of nAChRα-7., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pulmonary irritants, such as cigarette smoke (CS) and sodium hypochlorite (NaClO), are associated to pulmonary diseases in cleaning workers. We examined whether their association affects lung mechanics and inflammation in Wistar rats. Exposure to these irritants alone induced alterations in the lung mechanics, inflammation, and remodeling. The CS increased airway cell infiltration, acid mucus production, MMP-12 expression, and alveolar enlargement. NaClO increased the number of eosinophils and macrophages in the bronchoalveolar lavage fluid, with cells expressing IL-13, MMP-12, MMP-9, TIMP-1, and iNOS in addition to increased IL-1β and TNF-α levels. Co-exposure to both irritants increased epithelial and smooth muscle cell area, acid mucus production, and IL-13 expression in the airways, while it reduced the lung inflammation. In conclusion, the co-exposure of CS with NaClO reduced the pulmonary inflammation, but increased the acidity of mucus, which may protect lungs from more injury. A cross-resistance in people exposed to multiple lung irritants should also be considered. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is mainly caused by severe infection, shock, trauma, and burn, which causes the extensive release of inflammatory factors and other mediators. As a major bioactive constituent of traditional Chinese herb licorice, glycyrrhizic acid (GA) plays an important effect on inflammatory regulation. Nevertheless, the exact mechanism of this effect remains unclear. The present study aims to explore the potential protective effect of GA on LPS-induced ALI. Our results showed that GA significantly attenuated LPS-induced ALI and decreased the production of inflammatory factors, including IL-1β, MCP-1, COX2, HMGB1, and adhesion molecules, such as E-selectin, VCAM-1, and modulated expression of angiotensin-converting enzyme 2 (ACE2). Moreover, treatment of ACE2 inhibitor (MLN-4760) reversed the effects of GA on the secretion of pro-inflammatory factors in ALI. Additionally, GA exerts its protective effect by regulating the ACE2 and caveolin-1/NF-κB signaling pathway. In conclusion, this study showed that GA alleviated LPS-induced ALI by upregulating ACE2 and inhibiting the caveolin-1/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Esculetin, a coumarin derivative from various natural plants, has an anti-inflammatory property. In the present study, we examined if esculetin has any salutary effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Acute lung injury (ALI) was induced via the intratracheal administration of LPS, and esculetin (20 and 40 mg/kg) was given intraperitoneally 30 min before LPS challenge. After 6 h of LPS administration, lung tissues were collected for analysis. Pretreatment with esculetin significantly attenuated histopathological changes, inflammatory cell infiltration, and production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, in the lung tissue. Furthermore, esculetin inhibited the protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-κB) pathways and downregulated the expression of RORγt and IL-17 in LPS-induced ALI. Our results indicated that esculetin possesses anti-inflammatory and protective effects against LPS-induced ALI via inhibition of the AKT/ERK/NF-κB and RORγt/IL-17 pathways. [ABSTRACT FROM AUTHOR]