Our results implicate keratinocyte growth factor in the induction of alveolar epithelial cell proliferation for compensatory lung growth and indicate that overexpression of keratinocyte growth factor in the remaining lung by means of electroporation significantly augmented lung epithelial proliferation.
Our results suggest that D2-40 immunostaining provides a precise diagnosis of lymphatic vessel invasion, and our new grading system of vessel invasion by "degree" is accurate and has prognostic value in early lung cancer.
Objective. To clarify the significance of immunometabolism in systemic lupus erythematosus (SLE), and to determine the effect of calcium/calmodulin-dependent protein kinase 4 (CaMK4) on T cell metabolism.Methods. Metabolomic profiling was performed using capillary electrophoresis mass spectrometry in naive T cells from MRL/lpr mice treated with anti-CD3/CD28 antibodies in the absence or presence of a CaMK4 inhibitor (KN-93). The expression of GLUT1 and CaMK4 in CD4+ T cells from healthy controls (n = 16), patients with inactive SLE (n = 13), and patients with active SLE (n = 14) was examined by flow cytometry and quantitative polymerase chain reaction. In vitro experiments were performed to determine the effect of KN-93 on the expression of GLUT1 during Th17 cell differentiation in T cells from patients with SLE.Results. CaMK4 inhibition significantly decreased the levels of glycolytic intermediates such as glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate (P < 0.05), whereas it did not affect the levels of the pentose phosphate pathway intermediates such as 6-phosphod-gluconate, ribulose-5-phosphate, ribose-5-phosphate, and phosphoribosyl pyrophosphate. The expression levels of GLUT1 and CaMK4 in effector memory CD4+ T cells were significantly higher in patients with active SLE compared to healthy controls (P < 0.01 and P < 0.05, respectively) and patients with inactive SLE (P < 0.05 and P < 0.01, respectively). A functional analysis revealed that CaMK4 inhibition decreased the expression of GLUT1 during Th17 cell differentiation (P < 0.01), followed by a reduction of interleukin-17 (IL-17) production (P < 0.05).Conclusion. The results of the study indicate that the activity of CaMK4 could be responsible for glycolysis, which contributes to the production of IL-17, and CaMK4 may contribute to aberrant expression of GLUT1 in T cells from patients with active SLE.
Background
Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear.
Objectives
To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM‐ILD.
Methods
In total, 49 patients with PM/DM‐ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti‐MDA5 antibody, compared them between the RPILD (n = 23) and non‐RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL‐15 expression in lung tissues. The IL‐15 production was also investigated using A549 and BEAS‐2B cells.
Results
The RPILD group had significantly higher IL‐15, IL‐1RA, IL‐6, CXCL10, VCAM‐1, anti‐MDA5 antibody and ferritin serum levels than the non‐RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti‐MDA5 antibody, IL‐15, CXCL8, CCL22, IL‐1RA and ferritin were the best combination to distinguish the two groups. IL‐15 and CCL22 were also predictive marker for RPILD development in anti‐MDA5 antibody‐positive patients. Additionally, the RPILD group had significantly high IL‐15 levels in BALF. The lung tissues expressed IL‐15, which increased after cytokine stimulation in the A549 cells.
Conclusion
This study identified a combination of biomarkers predicting PM/DM‐RPILD progression, and IL‐15 is an important cytokine for predicting RPILD development and reflecting ILD severity.
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