Lipocalin-2 (LCN2) is an inflammatory mediator best known for its role as an innate acute-phase protein. LCN2 mediates the innate immune response to pathogens by sequestering iron, thereby inhibiting pathogen growth. Although LCN2 and its bacteriostatic properties are well studied, other LCN2 functions in the immune response to inflammatory stimuli are less well understood, such as its role as a chemoattractant and involvement in the regulation of cell migration and apoptosis. In the lungs, most studies thus far investigating the role of LCN2 in the immune response have looked at pathogenic inflammatory stimuli. Here, we compile data that explore the role of LCN2 in the immune response to various inflammatory stimuli in an effort to differentiate between protective versus detrimental roles of LCN2.

BACKGROUND: Respiratory diseases are one of the leading causes of death worldwide, yet effective treatment options remain limited. Although inflammation is thought to be a key driver in the pathogenesis and progression of several lung diseases, the underlying molecular mechanisms of lung dysfunction remain poorly understood. Imaging techniques may help to further our understanding of the pathophysiology and facilitate the translation of novel therapies. Positron Emission Tomography (PET) is a functional imaging technique which has the potential to interrogate the underlying inflammatory response. We present a systematic review of the literature summarising the emerging PET radiotracers developed to quantify pulmonary inflammation.
METHODS: We performed a systematic review using the following databases: Medline, Embase, Scopus, PubMed, Web of Science and Cochrane. We included articles between 1995 and 2019 for all studies using PET radiotracers to evaluate inflammatory response in the lung. From a total of 911 articles covering both animal and human studies, two reviewers selected papers based on the inclusion/exclusion criteria and extracted data from 68 articles selected.
RESULTS: 53 out of 68 papers, including both human and animal studies, were eligible for synthesis. Heterogenous study populations and differences in study design, image acquisition and analysis made data pooling unfeasible; instead, we provide a narrative synthesis.
CONCLUSIONS: Currently, very few novel radiotracers targeting lung inflammation have crossed the translational gap from animal models to human studies. Nevertheless, our results highlight a handful of promising tracers which warrant further evaluation in humans. 18F-FDG has been investigated most extensively; although 18F-FDG is not a specific inflammatory tracer, human studies of several pulmonary diseases support its use as a biomarker for inflammation. Despite ongoing debate about the optimal analysis methodology for 18F-FDG lung images, standardisation of image acquisition and analysis should help to improve confidence in research outcomes. PET radiotracers can provide quantitative, targeted biomarkers which relate to the activity of molecular pathways and may expedite development of specific anti-inflammatory drugs.

We performed a systematic review to identify and summarize the effects of distinctive aerobic exercise (AE) protocols on chronic allergic lung inflammation reported in asthma animal models. We identified 255 preclinical studies of asthma and AE protocols by comprehensive searches in PubMed, ScienceDirect and LILACS for peer-reviewed journals, using the search components \"exercise,\" \"lung inflammation,\" and \"asthma,\" without restrictions on publication date. Twenty-two studies were selected that met all eligibility criteria. Most studies used an ovalbumin experimental model and performed experiments with BALB/c mice. Most studies performed treadmill AE, using protocols of 30 to 60 minutes, 3 to 5 times/week, for 4 to 8 weeks. The results showed that the effects of AE on lungs were protocol dependent, but generaly, there was a decrease in inflammatory cell influx and Th2 cytokines, as well as an increase in anti-inflammatory defenses. However, the immunoregulation of globulins and nitric oxide levels in asthma seemed to be associated with the onset of AE. The results suggest that AE plays an important immunoregulatory role in animal models of asthma, with effects mainly mediated by increased anti-inflammatory defenses and reduced Th2 response. In parallel, prophylactic and therapeutic AE also played important roles in decreasing bronchial responsiveness and attenuating lung remodeling in animal models of asthma, secondary outcomes in this systematic review. The review protocol was published for free access in October 2017 on the Systematic Review Facility (SyRF) platform (http://syrf.org.uk/protocols/).

Inflammation is a physiological part of the complex biological response of tissues to counteract various harmful signals. This process involves diverse actors such as immune cells, blood vessels, and nerves as sources of mediators for inflammation control. Among them serine proteases are key elements in both physiological and pathological inflammation.
Serine protease inhibitors to treat inflammatory diseases are being actively investigated by various industrial and academic institutions. The present review covers patent literature on serine protease inhibitors for the therapy of inflammatory diseases patented between 2011 and 2016.
Serine proteases regulating inflammation are versatile enzymes, usually involved in proinflammatory cytokine production and activation of immune cells. Their dysregulation during inflammation can have devastating consequences, promoting various diseases including skin and lung inflammation, neuroinflammation, and inflammatory arthritis. Several serine proteases were selected for their contribution to inflammatory diseases and significant efforts that are spread to develop inhibitors. Strategies developed for inhibitor identification consist on either peptide-based inhibitor derived from endogenous protein inhibitors or small-organic molecules. It is also worth noting that among the recent patents on serine protease inhibitors related to inflammation a significant number are related to retinal vascular dysfunction and skin diseases.

Asthma, acute lung injury (ALI), and chronic obstructive pulmonary disease (COPD) are lung inflammatory disorders with a common outcome, that is, difficulty in breathing. Corticosteroids, a class of potent anti-inflammatory drugs, have shown less success in the treatment/management of these disorders, particularly ALI and COPD; thus, alternative therapies are needed. Poly(ADP-ribose)polymerases (PARPs) are the post-translational modifying enzymes with a primary role in DNA repair. During the last two decades, several studies have reported the critical role played by PARPs in a good of inflammatory disorders. In the current review, the studies that address the role of PARPs in asthma, ALI, and COPD have been discussed. Among the different members of the family, PARP-1 emerges as a key player in the orchestration of lung inflammation in asthma and ALI. In addition, PARP activation seems to be associated with the progression of COPD. Furthermore, PARP-14 seems to play a crucial role in asthma. STAT-6 and GATA-3 are reported to be central players in PARP-1-mediated eosinophilic inflammation in asthma. Interestingly, oxidative stress-PARP-1-NF-κB axis appears to be tightly linked with inflammatory response in all three-lung diseases despite their distinct pathophysiologies. The present review sheds light on PARP-1-regulated factors, which may be common or differential players in asthma/ALI/COPD and put forward our prospective for future studies.