Bronchoprotective mechanisms for specialized pro-resolving mediators in the resolution of lung inflammation

Abstract

Bronchi are exposed daily to irritants, microbes and allergens as well as extremes of temperature and acid. The airway mucosal epithelium plays a pivotal role as a sentinel, releasing alarmins when danger is encountered. To maintain homeostasis, an elaborate counter-regulatory network of signals and cellular effector mechanisms are needed. Specialized pro-resolving mediators (SPMs) are chemical mediators that enact resolution programs in response to injury, infection or allergy. SPMs are enzymatically derived from essential polyunsaturated fatty acids with potent cell-type specific immunoresolvent properties. SPMs signal by engaging cell-based receptors to turn off acute inflammatory responses and restore tissue homeostasis. Several common lung diseases involving the airways, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), are characterized by unresolved bronchial inflammation. In preclinical murine models of lung disease, SPMs carry potent bronchoprotective actions. Here, we review cellular and molecular effects for SPM-initiated catabasis in the lung and their human translation.

Deep Airway Inflammation and Respiratory Disorders in Nanocomposite Workers

“…We have extended our previous investigation on lung injury in workers exposed to aerosols containing 80–85% nanoparticles of TiO 2 or Fe-oxides to nanocomposite researchers and we have shown that nanocomposites workers have high markers of oxidative stress in EBC [ 24 ]. In this study of researchers involved in various steps of nanocomposite synthesis and processing during the research and development phase, we have expanded our repertoire of biomarkers to also include several pro-inflammatory cytokines/chemokines (TNF, IL 5, and IL 9), as well as anti-inflammatory IL 4, IL 10, and IL 13, and lipoxins LXA4 and LXB4 [ 25 ] in EBC. These cytokines/chemokines stimulate the growth, differentiation, and recruitment of mast cells, eosinophils, basophils, and B-cells, all of which are involved in humoral immunity and allergic responses.…”

Markers of oxidative stress after three days of nanoTiO₂ sunscreen use in humans: a pilot study

“…Differently, no EBC markers were elevated in this study, and no positive trend was noted. Some elevations in our previous study concerned especially LTs, inflammation markers that may reflect subclinical inflammation in the respiratory system, as they are involved in the response to injury, infection, or allergy (27)(28)(29). Therefore, markers in EBC usually reflect occupational exposures of workers to nanomaterials by inhalation (30)(31)(32)(33)(34), including office employees exposed to nanoTiO 2 (35).…”

Granulocyte-targeted therapies for airway diseases

“…SPMs mainly act through binding to receptors in cell surface. Of note, eosinophils, neutrophils, mast cells and lung epithelial cells express SPM receptors being able to produce and respond to these molecules [120]. A proper resolution of inflammation assures the reduction of secretion of pro-inflammatory mediators and recruitment of granulocytes while increases clearance of apoptotic cells and induces tissue repair responses [119].…”