Comparing the expression of MiR-223-NLRP3-IL-1ß axis and serum IL-1ß levels in patients with severe COVID-19 and healthy individuals.

BACKGROUND AND AIM: The hyperactive nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor for cytokine storm, chronic inflammation, and mortality in infected patients. On the subject of the regulation of the NLRP3-inflammasome activation, micro-ribonucleic acid (RNA)-223 (miR-223), among the major RNA molecules, has been thus far investigated in some inflammatory diseases along with interleukin-1 beta (IL-1ß) and NLRP3. Against this background, the present study aimed to compare healthy individuals and patients with severe COVID-19 with reference to the alterations in the expression of the miR-223, NLRP3, and IL-1ß axis and the serum IL-1ß levels. METHODS: In total, 40 patients with severe COVID-19, admitted to the Infectious Ward of Razi Hospital, Ahvaz, Iran, who were homogenous in terms of age (40 years old) and gender, were selected based on the inclusion and exclusion criteria. The real-time polymerase chain reaction (RT-PCR) technique was then applied to assess the expression of the miR-223, NLRP3, and IL-1ß genes, and enzyme-linked immunosorbent assay (ELISA) was then utilized to evaluate the serum IL-1ß levels, using patients' blood samples. Moreover, inflammatory biochemical markers of the participants were collected and recorded RESULTS: According to the study results, the IL-1ß expression was 3.9 times higher in the patients with COVID-19, compared with the control group (p = 0.0005). The NLRP3 expression was also 6.04 times greater in the infected patients, compared with the healthy individuals (p < 0.0001). On the other hand, the miR-223 expression was 5.37 times lower in the case group, compared with the controls (p = 0.04). CONCLUSION: The study findings indicated the potential role of miR-223 and the dysregulation of NLRP3 inflammasome followed by IL-1ß, as a regulatory factor in the pathogenesis of COVID-19, like that in other inflammatory diseases.

miRNA-223 as a regulator of inflammation and NLRP3 inflammasome, the main fragments in the puzzle of immunopathogenesis of different inflammatory diseases and COVID-19.

Millions of people around the world are involved with COVID-19 due to infection with SARS-CoV-2. Virological features of SARS-CoV-2, including its genomic sequence, have been identified but the mechanisms governing COVID-19 immunopathogenesis have remained uncertain. miR-223 is a hematopoietic cell-derived miRNA that is implicated in regulating monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses. The miR-223 controls inflammation by targeting a variety of factors, including TRAF6, IKKα, HSP-70, FOXO1, TLR4, PI3K/AKT, PARP-1, HDAC2, ITGB3, CXCL2, CCL3, IL-6, IFN-I, STMN1, IL-1ß, IL-18, Caspase-1, NF-κB, and NLRP3. The key role of miR-223 in regulating the inflammatory process and its antioxidant and antiviral role can suggest this miRNA as a potential regulatory factor in the process of COVID-19 immunopathogenesis.

Tranilast: a potential anti-Inflammatory and NLRP3 inflammasome inhibitor drug for COVID-19.

SARS-CoV-2 is a type of beta-CoV that develops acute pneumonia, which is an inflammatory condition. A cytokine storm has been recognized as one of the leading causes of death in patients with COVID-19. ALI and ARDS along with multiple organ failure have also been presented as the consequences of acute inflammation and cytokine storm. It has been previously confirmed that SARS-CoV, as another member of the beta-CoV family, activates NLRP3 inflammasome and consequently develops acute inflammation in a variety of ways through having complex interactions with the host immune system using structural and nonstructural proteins. Numerous studies conducted on Tranilast have further demonstrated that the given drug can act as an effective anti-chemotactic factor on controlling inflammation, and thus, it can possibly help the improvement of the acute form of COVID-19 by inhibiting some key inflammation-associated transcription factors such as NF-κB and impeding NLRP3 inflammasome. Several studies have comparably revealed the direct effect of this drug on the prevention of inappropriate tissue's remodeling; inhibition of neutrophils, IL-5, and eosinophils; repression of inflammatory cell infiltration into inflammation site; restriction of factors involved in acute airway inflammation like IL-33; and suppression of cytokine IL-13, which increase mucosal secretions. Therefore, Tranilast may be considered as a potential treatment for patients with the acute form of COVID-19 along with other drugs.

Interleukin-22 and intestinal homeostasis: Protective or destructive?

Interleukin (IL)-22 is a member of IL-10 family cytokines with various immunologic functions. As its name implies, IL-22 is known to be secreted mainly by Th22 cells, a recently discovered lineage of CD4+ T cells. Also, Th17, Th1, natural killer cells, γδT cells, and innate immune cells along with some nonlymphoid cells have been confirmed as secondary cellular sources of IL-22. Different cell types such as bronchial and intestinal epithelial cells, keratinocytes, hepatocytes, dermal fibroblasts, and tubular epithelial cells are affected by IL-22. Both pathologic and protective roles have been attributed to IL-22 in maintaining gut homeostasis and inflammation. According to the latest fast-growing investigations, IL-22 is significantly involved in various pathologies including allergic diseases, infection, autoimmunity, and cancer development. Regulating gut immune responses, barrier integrity, and inflammation is dependent on a diverse complex of cytokines and mediators which are secreted by mucosal immune cells. Several investigations have been designed to recognize the role of IL-22 in gastrointestinal immunity. This article tries to discuss the latest knowledge on this issue and clarify the potential of IL-22 to be used in the future therapeutic approaches of intestinal disorders including inflammatory bowel diseases and colon cancer.