Mouse Anti Human ICAM-1 Hybridoma [Q3B5]

Objective: Endothelial cellular senescence is an important contributor to the endothelial dysfunction and atherosclerosis. Our previous studies suggested that salidroside (SAL) can alleviate atherosclerosis and protect endothelial cells against oxidative stress induced damage. However, the effect and mechanism of SAL on endothelial cellular senescence is still unclear. Here, we investigated the underlying mechanisms of SAL on preventing endothelial cellular premature senescence. Methods and results: We established a hyperhomocysteinemia (HHcy)mouse model via high methionine diet (HMD) to explore the protective effect of SAL. According to our results, the HMD elevated the concentration of serum homocysteine. HHcy induced the collagen deposition and the up-regulation of senescence markers, i.e. p16(INK4A) and p21(CIP1), in intima-medial of aorta. In addition, SAL also inhibited the expression of CD68 and intercellular adhesion molecule 1 (ICAM1) in aorta. In senescent human umbilical vein endothelial cells (HUVECs) induced by H2O2, SAL treatment alleviated the expression of p16(INK4A) and p21(CI)(P1) and reduced the activity of senescence-associated (SA)-beta-gal. Conclusion: our data suggested that SAL decreased the expression of inflammatory cytokines and up-regulated the expression of SIRT3, which might be the underlying mechanism of SAL on preventing endothelial cells from premature senescence.

Intratumoral formation of tertiary lymphoid structures (TLS) within the tumor microenvironment is considered to be a consequence of antigen challenge during anti-tumor responses. Intracellular adhesion molecule 1 (ICAM1) has been implicated in a variety of immune and inflammatory responses, in addition to associate with triple negative breast cancer (TNBC). In this study, we detected TLS in the aggressive tumor phenotypes TNBC, HER2+ and luminal B, whereas the TLS negative group contained solely tumors of the luminal A subtype. We show that ICAM1 is exclusively expressed in TNBC and HER2 enriched subtypes known to be associated with inflammation and the formation of TLS. Furthermore, cell from normal mammary epithelium and breast cancer cell lines expressed ICAM1 upon stimulation with the proinflammatory cytokines TNF alpha, IL1 beta and IFN gamma. ICAM1 overexpression was induced in MCF7, MDA-MB-468 and SK-BR-3 cells regardless of hormone receptor status. Taken together, our findings show that ICAM1 is expressed in aggressive subtypes of breast cancer and its expression is inducible by well-known proinflammatory cytokines. ICAM1 may be an attractive molecular target for TNBC, but further investigations elucidating the role of ICAM1 in targeted therapies have to take into consideration selective subtypes of breast cancer.