Objective To investigate the expressions of interleukin (IL)-21 and phosphorylated extracellular signal regulated kinase 1/2 ( pERK1/2) in Kimura disease (KD) and to correlate the findings with clinical and prognostic variables. Methods Immunohistochemical analysis of IL-21 and pERK1/2 was performed in 18 cases of KD and five gender-and age-matched control samples. Clinical data were extracted and patients followed up for a mean period of 32.1 months.Results After a mean follow-up period of 32.1 months (range 1-102 months), recurrence was diagnosed as the end point for seven patients-that is, a 44% (7/16) cumulative recurrence rate. In comparison with genderand age-matched controls, patients showed strong in situ expressions of IL-21 and pERK1/2, respectively ( p<0.05). Patients with strong IL-21 staining intensity and overexpression of pERK1/2 had a lower recurrence rate than those with moderate staining intensity ( p=0.049, p=0.019, respectively). However, differences were not statistically significant by gender, age, eosinophils, location, multiplicity, laterality, size, duration and primary outbreak. pERK1/2 was the independent prognostic factor ( p=0.020), while age, gender, eosinophils, multiplicity, laterality, size, duration, primary outbreak and expression of IL-21 were not. Conclusions This study suggests that the IL-21/pERK1/ 2 pathway is activated in KD, and pERK1/2 might be considered as a potential prognostic indicator in KD.
Objective Septic liver injury is a major burden for the clinical management of sepsis. Hepatocyte cell death plays a crucial pathophysiological role in sepsis. A recent study proposed that NLRP3 inflammasome-mediated pyroptosis participates in septic liver injury. Therefore, investigating the mechanism controlling this process may help manage sepsis. Methods We investigated the role of homeodomain-interacting protein kinase 2 (HIPK2) in regulating the NLRP3 inflammasome in vivo using mouse models and in vitro in primary hepatocytes. Results HIPK2 could improve liver injury and survival in a mouse model of sepsis. Overexpression of HIPK2 could suppress NLRP3 and caspase-1-p20 expression, while HIPK2 knockdown led to higher levels of these two molecules. Importantly, HIPK2 could suppress endoplasmic reticulum (ER) stress. Pharmacologically inhibiting ER stress could abolish activation of the NLRP3 inflammasome in hepatocytes with HIPK2 knockdown. Conclusion HIPK2 can regulate ER stress and NLRP3 inflammasome activation in the liver during sepsis, and HIPK2-mediated suppression of ER stress participates in regulating NLRP3 inflammasome activation. The present study highlights the role of HIPK2 in regulating the inflammasome in septic liver injury, which may serve as a target for managing sepsis.
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