Cigarette smoke is the primary cause of Chronic Obstructive Pulmonary Disorder (COPD). Cigarette smoke extract (CSE)-induced oxidative damage of the lungs results in mitochondrial dysfunction and apoptosis of epithelium. Mitochondrial cardiolipin (CL) present in the inner mitochondrial membrane plays an important role in mitochondrial function, wherein its fatty acid composition is regulated by lysocardiolipin acyltransferase (LYCAT). In this study, we investigated the role of LYCAT expression and activity in mitochondrial oxidative stress, mitochondrial dynamics, and lung epithelial cell apoptosis. LYCAT expression was increased in human lung specimens from smokers, and cigarette smoke-exposed-mouse lung tissues. Cigarette smoke extract (CSE) increased LYCAT mRNA levels and protein expression, modulated cardiolipin fatty acid composition, and enhanced mitochondrial fission in the bronchial epithelial cell line, BEAS-2B in vitro. Inhibition of LYCAT activity with a peptide mimetic, attenuated CSE-mediated mitochondrial (mt) reactive oxygen species (ROS), mitochondrial fragmentation, and apoptosis, while MitoTEMPO attenuated CSE-induced MitoROS, mitochondrial fission and apoptosis of BEAS-2B cells. Collectively, these findings suggest that increased LYCAT expression promotes MitoROS, mitochondrial dynamics and apoptosis of lung epithelial cells. Given the key role of LYCAT in mitochondrial cardiolipin remodeling and function, strategies aimed at inhibiting LYCAT activity and ROS may offer an innovative approach to minimize lung inflammation caused by cigarette smoke.

Role of Lysocardiolipin Acyltransferase in Cigarette Smoke-Induced Lung Epithelial Cell Mitochondrial ROS, Mitochondrial Dynamics, and Apoptosis

Preterm birth is a major contributor to neonatal mortality and morbidity. Infection results in elevation of inflammation‐related cytokines followed by infiltration of immune cells into gestational tissue. CXCL12 levels are elevated in preterm birth indicating it may have a role in preterm labour (PTL); however, the pathophysiological correlations between CXCL12/CXCR4 signalling and premature labour are poorly understood. In this study, PTL was induced using lipopolysaccharide (LPS) in a murine model. LPS induced CXCL12 RNA and protein levels significantly and specifically in myometrium compared with controls (3‐fold and 3.5‐fold respectively). Highest levels were found just before the start of labour. LPS also enhanced the infiltration of neutrophils, macrophages and T cells, and induced macrophage M1 polarization. In vitro studies showed that condition medium from LPS‐treated primary smooth muscle cells (SMC) induced macrophage migration, M1 polarization and upregulated inflammation‐related cytokines such as interleukin (IL)‐1, IL‐6 and tumor necrosis factor alpha (TNF‐α). AMD3100 treatment in pregnant mice led to a significant decrease in the rate of PTL (70%), prolonged pregnancy duration and suppressed macrophage infiltration into gestation tissue by 2.5‐fold. Further, in‐vitro treatment of SMC by AMD3100 suppressed the macrophage migration, decreased polarization and downregulated IL‐1, IL‐6 and TNF‐α expression. LPS treatment in pregnant mice induced PTL by increasing myometrial CXCL12, which recruits immune cells that in turn produce inflammation‐related cytokines. These effects stimulated by LPS were completely reversed by AMD3100 through blocking of CXCL12/CXCR4 signalling. Thus, the CXCL12/CXCR4 axis presents an excellent target for preventing infection and inflammation‐related PTL.

Myometrial‐derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice

The present study aimed to investigate the mechanism of penile damages in experimental autoimmune prostatitis (EAP) rat models to reveal the potential pathological mechanism of the relationship between CP and penile damages. Sprague-Dawley (SD) rats were administered with different concentrations of prostate tissue homogenate supernatant (PTHS) by multipoint subcutaneous injection to establish EAP models. IHC staining was done to assess the expression of inflammatory cytokines in prostate tissues and the corpus cavernosum of penis. Masson and Tunel staining was conducted to observe the fibrosis and apoptosis in the corpus cavernosum. Finally, the functional changes of corpus cavernosum were assessed by WB and IHC staining. The results revealed that EAP rats with different prostatitis severity were successfully established by PTHS. The expression of IL-1β, IL-6 and TNF-α in prostate tissues increased with the concentration of PTHS. The results of Masson and Tunel staining indicated fibrosis and apoptosis gradually aggravated in corpus cavernosum among different subgroups. The function of cavernosum impaired by prostatitis from WB and IHC results and positively with the severity. In conclusion, there existed the infiltration of inflammatory factors and impaired function in the corpus cavernosum of EAP rats' penis and positively correlated with the severity of prostatitis.

Infiltration of inflammatory factors induced penile damage in chronic prostatitis.

The intervention effect of nicotine on cervical fibroblast-myofibroblast differentiation in lipopolysaccharide-induced preterm birth model through activating the TGF-β1/Smad3 pathway.

Jinying Yang

Papers

The intervention effect of nicotine on cervical fibroblast-myofibroblast differentiation in lipopolysaccharide-induced preterm birth model through activating the TGF-β1/Smad3 pathway.