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Purpose Recent studies have demonstrated that macrophage migration inhibitory factor (MIF) is of importance in asthmatic inflammation. The role of MIF in modulating airway remodeling has not yet been thoroughly elucidated to date. In the present study, we hypothesized that MIF promoted airway remodeling by intensifying airway smooth muscle cell (ASMC) autophagy and explored the specific mechanisms. Methods MIF knockdown in the lung tissues of C57BL/6 mice was conducted by instilling intratracheally adeno-associated virus (AAV) vectors (MIF-mutant AAV9) into mouse lung tissues. Mice genetically deficient in the autophagy marker ATG5 (ATG5 +/− ) was used to detect the role of autophagy in ovalbumin (OVA)-asthmatic murine models. Moreover, to block the expression of MIF and CD74 in vitro models, inhibitors, antibodies and lentivirus transfection techniques were employed. Results First, MIF knockdown in the lung tissues of mice showed markedly reduced airway remodeling in OVA murine mice models. Secondly, ASMC autophagy was increased in the OVA-challenged models. Mice genetically deficient in the autophagy marker ATG5 (ATG5 +/− ) that were primed and challenged with OVA showed lower airway remodeling than genetically wild-type asthmatic mice. Thirdly, MIF can induce ASMC autophagy in vitro . Moreover, the cellular source of MIF which promoted ASMC autophagy was macrophages. Finally, MIF promoted ASMC autophagy in a CD74-dependent manner. Conclusions MIF can increase asthmatic airway remodeling by enhancing ASMC autophagy. Macrophage-derived MIF can promote ASMC autophagy by targeting CD74.

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of autoimmune nature, characterized by painful, swollen joints that can severely impair physical function and quality of life. 1,2 The disease affects women 2-3 times more often than men and occurs at any age. 3 The peak incidence is between ages 50-60 years. In Western countries, the prevalence of RA is in the range of 0.5%-1.0% in White individuals, while the prevalence ratios were 0.45, 0.69 and 1.02 for women of Hispanic, Asian or African-American descent,

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We aimed to evaluate the clinical relevance of serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) in stable COPD patients. The expression of serum 14-3-3β protein was evaluated by an enzyme-linked immunosorbent assay. The association between its concentrations and clinical parameters of stable COPD patients were analyzed by correlation analysis and ROC curve. The results before propensity score matching (PSM) showed that serum 14-3-3β protein concentrations (ng/ml) in stable COPD patients were significantly higher than in healthy controls (P<0.001). Furthermore, serum 14-3-3β protein concentrations were higher in GOLD 3&4 COPD patients compared with healthy participants, GOLD 1 and GOLD 2 COPD patients (P<0.05). After 1:1 PSM, there was also a statistically significant rise in 14-3-3 protein levels in stable COPD patients compared to healthy controls (P<0.01). Serum 14-3-3β protein levels were positively correlated with blood neutrophil levels (P<0.05), and negatively related to lung function parameters in stable COPD patients (P<0.01). When the cutoff value was set at 29.53ng/ml, the ROC curve yielded a sensitivity of 84.9% and a specificity of 68.3% for diagnosing stable COPD. The 14-3-3β protein may be a potential serum biomarker that was associated with disease severity, systemic inflammation, and small airway obstruction in stable COPD patients.