Circulating level of high mobility group box-1 predicts the severity of community-acquired pneumonia: Regulation of inflammatory responses via the c-Jun N-terminal signaling pathway in macrophages

Abstract

High mobility group box-1 (HMGB-1) has been reported to serve significant roles in various inflammatory diseases. However, the correlation between the circulating level of HMGB-1 and severity of community-acquired pneumonia (CAP) remains unclear. The present study investigated differential alterations in plasma HMGB-1 levels of patients with CAP prior to and following antibiotic treatment, and further analyzed the association between CAP severity and HMGB-1 levels. Furthermore, lipopolysaccharide (LPS)-induced HMGB-1 expression in RAW264.7 macrophages and the relevant signaling pathways were examined. Plasma HMGB-1 levels of 90 patients with CAP and 52 healthy controls were measured using a commercial ELISA. The levels of plasma HMGB-1 were significantly elevated in CAP patients compared with the controls, and antibiotic treatment was effective in reducing HMGB-1 levels. Plasma HMGB-1 correlated with the pneumonia severity index score (r=0.566, P<0.001). Furthermore, LPS-stimulation significantly upregulated HMGB-1 secretion via the c-Jun N-terminal kinase (JNK) signaling pathway in RAW264.7 macrophages, whereas pretreatment with the JNK inhibitor SP600125 markedly downregulated LPS-induced HMGB-1 levels. In conclusion, plasma HMGB-1 levels may serve a role in the diagnosis and clinical assessment of CAP severity. These findings may provide information on novel targets for the treatment of CAP.

Plasma Soluble Urokinase-Type Plasminogen Activator Receptor Level as a Predictor of the Severity of Community-Acquired Pneumonia

“…The RAW 264.7 macrophage cell lines were purchased from ATCC (Manassas, VA, USA). The RAW 264.7 macrophage cell lines was cultured in Dulbecco’s modified Eagle’s medium with 10% fetal bovine serum as previously described [13]. All cell cultures were maintained at 37 °C in a humidified atmosphere of 5% CO 2 .…”

Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19?

“…Extracellular HMGB1 levels were elevated in all patients with community-acquired pneumonia and higher circulating HMGB1 was associated with disease severity and mortality (Angus et al 2007;Wang et al 2017).…”

High HMGB1 levels in sputum are related to pneumococcal bacteraemia but not to disease severity in community-acquired pneumonia

“… 10 shows similar plasma HMGB1 levels to our study, whereas the study by Wang et al . 9 shows lower levels. Standardisation of the methods of measuring circulating levels and airway levels of HMGB1 is needed for further research and/or clinical use.…”

“… 10 , in which similar HMGB1 levels in uncomplicated pneumonia and pneumonia with sepsis were found, but conflict with the result of Wang et al . 9 , who found HMGB1 to be correlated to PSI risk class. It is difficult to compare our study with the Wang study, as their study lacked information about X-ray findings, comorbidity, and aetiological information.…”

“…Wang et al . 9 studied plasma HMGB1 levels in 90 patients with suspected community-acquired pneumonia (CAP) and found that it correlated to disease severity, with higher levels in higher pneumonia severity index (PSI) risk classes. Meanwhile, in a study by Angus et al .…”