Alarmins and MicroRNAs, a New Axis in the Genesis of Respiratory Diseases: Possible Therapeutic Implications

Abstract

It is well ascertained that airway inflammation has a key role in the genesis of numerous respiratory pathologies, including asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome. Pulmonary tissue inflammation and anti-inflammatory responses implicate an intricate relationship between local and infiltrating immune cells and structural pulmonary cells. Alarmins are endogenic proteins discharged after cell injury in the extracellular microenvironment. The purpose of our review is to highlight the alterations in respiratory diseases involving some alarmins, such as high mobility group box 1 (HMGB1) and interleukin (IL)-33, and their inter-relationships and relationships with genetic non-coding material, such as microRNAs. The role played by these alarmins in some pathophysiological processes confirms the existence of an axis composed of HMGB1 and IL-33. These alarmins have been implicated in ferroptosis, the onset of type 2 inflammation and airway alterations. Moreover, both factors can act on non-coding genetic material capable of modifying respiratory function. Finally, we present an outline of alarmins and RNA-based therapeutics that have been proposed to treat respiratory pathologies.

Gender Differences and miRNAs Expression in Cancer: Implications on Prognosis and Susceptibility

“…MicroRNAs are small, noncoding molecules of about twenty-two nucleotides and have crucial roles in both healthy and pathological cells; in fact, they are involved in various intra-and intercellular mechanisms like proliferation and apoptosis, so their incorrect function is involved in the onset of different diseases, such as cancer [1,2]. In detail, a miRNA could have a lot of genes as targets and, at the same time, a gene could be regulated by different miRNAs [3]; according to the scientific literature, they control about 60% of human genes [4].…”

Emerging Role of Alarmins in Food Allergy: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications

“…IL-33 drives Th2-associated cytokine production in children [ 40 ] and adults [ 41 ] with allergic asthma. In addition, some authors have demonstrated its role in food allergy.…”

“…Studies on humans confirmed the importance of alarmins in IgE-mediated allergies: serum concentrations of TSLP and IL-25 are found to be increased in patients with food allergy [ 40 ], and IL-25 levels appear to correlate positively with atopic severe phenotypes [ 43 ]. TSLP and IL-33 could also play a role in the development of tolerance in humans [ 41 ], and their expression in the oral mucosa would be influenced by the microbiome [ 42 ]. Fecal calprotectin levels appear to be significantly elevated in patients with food allergies, which decrease after an exclusion diet [ 46 ].…”

High‐mobility group box 1 emerges as a therapeutic target for asthma

“…[79][80][81] HMGB1 levels were negatively correlated with lung function in asthmatic patients. [82][83][84] This means that HMGB1 may be a potential biomarker of asthma severity. 85 In addition, inhibition of HMGB1 protects human bronchial epithelial cells (HBE) by alleviating TDI-induced asthma via ROS/AMPK/autophagy pathway.…”

“…It is reported that HMGB1 levels in sputum of asthmatic patients are significantly increased and positively correlated with asthma severity, obesity, and neutrophil percentage and significantly increased in lung tissue and bronchoalveolar lavage fluid (BALF) of asthmatic rats induced by ovalbumin (OVA) and positively correlated with obesity 79–81 . HMGB1 levels were negatively correlated with lung function in asthmatic patients 82–84 . This means that HMGB1 may be a potential biomarker of asthma severity 85 .…”