Magic™ Anti-IGF1R (C-terminal)(phospho Y1161) polyclonal antibody

Objectives: Oral lichen planus (OLP) is a T cell-mediated immune-related chronic disease, featured by accumulation of T cells and apoptosis of keratinocytes. Insulin-like growth factors 1 (IGF1) signaling, in combination with its downstream PI3K/AKT/MTOR cascade, plays pivotal roles in the regulation of inflammation and immune response. Meanwhile, TRB3 acts as a connective protein in the pathway. This study investigated the possible function of IGF1-PI3K/AKT/MTOR pathway in the local immunity of OLP. Methods: The expression of phosphorylated IGF1R (p-IGF1R) and TRB3 in lesional tissues of OLP was measured. The effects of T cells pretreated with PI3K inhibitor LY294002, MTOR antagonist rapamycin and exogenous IGF1 on the cell proliferation and apoptosis, as well as supernatant inflammatory cytokine levels were detected in co-culture system of activated T cells and oral keratinocytes, respectively. Results: The expression of p-IGF1R and TRB3 in OLP lesions was significantly increased when compared with controls (P < 0.001). Rapamycin-treated T cells displayed enhanced apoptosis rate and promoted proliferation of their keratinocytes in the co-culture system. Notably, abnormal expression of IFN-gamma and IL-4 were detected in supernatant of T cell alone and co-culture system in response to pharmacological modulators of IGF1-PI3K/MTOR pathway. Conclusions: The aberrant IGF1-PI3K/AKT/MTOR signaling may participate in the immunoregulatory mechanism of OLP, via regulation on the crosstalk between T cells and keratinocytes, as well as imbalanced cytokine networks.

Background/Aim Hypertensive cardiac hypertrophy is the leading cause of cardiac remodeling and heart failure. We recently demonstrated that the immunoproteasome, an inducible form of the constitutive proteasome, plays a critical role in regulating cardiovascular diseases. However, the role of the immunoproteasome LMP10 (beta 2i) catalytic subunit in the regulation of angiotensin II (Ang II)-induced cardiac hypertrophic remodeling remains unclear. Methods Wild-type (WT) and LMP10 knockout (KO) mice were infused with Ang II 1,000 ng/kg/min for 2 weeks. Blood pressure was measured using a tail-cuff system. Cardiac function and hypertrophic remodeling were examined by echocardiography and histological staining. The expression levels of genes and proteins were examined with quantitative real-time PCR and immunoblotting analysis, respectively. Results LMP10 mRNA and protein expression was significantly increased in Ang II-stimulated hearts and primary cardiomyocytes. Moreover, Ang II infusion for 2 weeks increased systolic blood pressure, abnormal cardiac function, hypertrophy, fibrosis, and inflammation in WT mice, which were significantly reversed in KO mice. Moreover, a marked reduction in the protein levels of insulin growth factor-1 receptor (IGF1R), glycoprotein 130 (gp130), and phosphorylated AKT, mTOR, STAT3, and ERK1/2 and an increase in the LC3II/I ratio were also observed in LMP10 KO mice compared with WT mice after Ang II infusion.In vitroculture experiments confirmed that LMP10 knockdown activated autophagy and increased IGF1R and gp130 degradation, leading to the inhibition of cardiomyocyte hypertrophy. However, inhibiting autophagy with chloroquine reversed this effect. Conclusion The results of this study indicate that LMP10 KO attenuates Ang II-induced cardiac hypertrophic remodeling via the autophagy-dependent degradation of IGF1R and gp130, and suggests that LMP10 may be a novel therapeutic target for hypertrophic heart diseases.