Combination of azithromycin and methylprednisolone alleviates Mycoplasma pneumoniae induced pneumonia by regulating miR‑499a‑5p/STAT3 axis

Abstract

Mycoplasma pneumoniae ( M. pneumoniae ) is a contributing factor to community-acquired pneumonia in children. The present study sought to explain the underlying mechanism of azithromycin (AZM) combined with methylprednisolone (MP) in the treatment of M. pneumoniae infection. Peripheral blood samples were obtained from patients with M. pneumoniae and healthy volunteers for analysis. A549 cells were infected with M. pneumoniae to construct an in vitro cell model with M. pneumoniae , followed by treatment with AZM and MP. Cell Counting Kit-8 and TUNEL assays were conducted to detect cell viability and apoptosis. RT-qPCR was employed to measure the expression levels of microRNA (miR)-499a-5p and STAT3. Western blotting was performed to measure the expression of STAT3 and apoptosis-related proteins. Luciferase report assay was performed to verify the binding site between miR-499a-5p and STAT3. The production of inflammatory cytokines was determined using ELISA kits. The results exhibited the downregulated miR-499a-5p and dysregulated inflammatory cytokines in peripheral blood of patients and M. pneumoniae -infected A549 cells. AZM and MP treatment alone or combined significantly inhibited inflammatory response, cell viability loss and promoted apoptosis in A549 cells infected with M. pneumoniae , which was partly reversed by inhibition of miR-499a-5p. Furthermore, miR-499a-5p could negatively regulate its direct target STAT3. In addition, STAT3 is also regulated by AZM and MP. Collectively, the present results suggested that combination treatment of AZM and MP could inhibit M. pneumoniae infection-induced inflammation, cell viability loss and promoted apoptosis partly by regulating miR-499a-5p/STAT3 axis.

Clinical significance of serum microRNA-146a and inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment

“… 24 Azithromycin treatment has been shown to suppress M. pneumoniae infection-elicited inflammation, decrease cell viability, and inhibit apoptosis, partially through the modulation of the miR-499a-5p/STAT3 axis. 25 Collectively, these findings suggest that targeting miR-146a and pro-inflammatory cytokines could hold promise for azithromycin therapy in MPP.…”

ITRAQ-based quantitative proteomics analysis of forest musk deer with pneumonia

“…Among the cancer-related proteins, signal transducer and activator of transcription 3 (STAT3) has been well documented to be inflammation and immunity ( 62 – 64 ). Also, STAT3 served as a positive regulator of pneumonia induced by influenza virus H1N1 ( 65 ), Agiostrongylus cantonensis ( 66 ), and Mycoplasma pneumonia ( 67 ). Combined with these data, we supposed that dysregulated proteins related to amoebiasis and cancer might also function as crucial players in pneumonia, immune, and inflammation, suggesting the same or like immune response activity between pneumonia and amoebiasis or cancer.…”

The Effect of Methylprednisolone Combined With Macrolide Antibiotics on Mycoplasma Pneumoniae Pneumonia in Children

“…In addition, the score on the quality of life of the children in the experimental group after treatment was higher than that of the control group, which showed that the MP + MA could quickly alleviate the patient's clinical symptoms and adverse physical signs, promote the mental state of patients and improve the quality of life, shorten the length of hospitalization, and improve their survival. Regarding the mechanism through which the combination of MA and MP can better inhibit Mycoplasma pneumonie infection-induced inflammation, new in vitro studies have shown their implication in the regulation of miR-499a-5p/STAT3 axis [16]. Mycoplasma pneumonie infection can up-regulate STAT3-mediated signalling pathway [17] that is involved in inflammation and down-regulate the levels of miR-499a-5p that is involved in alleviating inflammation in infection-related diseases [18].…”