Induction of intercellular adhesion molecule-1 expression in human melanoma cell lines by hyperthermia in vitro and in vivo

The role of intercellular adhesion molecule-1 (ICAM-1) in murine lung inflammation was examined in vivo. Ovalbumin (Ova)-sensitized and -challenged ICAM-1-deficient (KO) mice had decreased accumulation of leukocytes in the bronchoalveolar lavage fluid compared with wild-type (WT) mice. Lung tissue inflammation was also attenuated. Ova immunization and challenge produced equivalent plasma levels of Ova-specific immunoglobulin (Ig) G1 and higher concentrations of IgE in KO versus WT mice. Ova-dependent induction of cytokines in vitro, as measured by enzyme-linked immunosorbent assay, was impaired in splenocytes from KO mice compared with the comparable release of interleukin (IL)-5 and IL-10 from anti-CD3-stimulated WT and KO splenocytes. Methacholine-induced increases in trapped gas in lungs of Ova-sensitized and -challenged WT mice were greater than those of KO mice. The activation of lung tissue nuclear factor-kappa B was diminished in KO mice after Ova provocation. This suggests that ICAM-1 was important for activation of the inflammatory cascade leading to the recruitment of leukocytes but was not critical for the generation of antibody responses in vivo.

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Role of Flavonoids in the Prevention of AhR-Dependent Resistance During Treatment with BRAF Inhibitors

International Journal of Molecular Sciences ◽

10.3390/ijms21145025 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5025

Author(s):

Héloïse M. Leclair ◽

Nina Tardif ◽

Anaïs Paris ◽

Marie-Dominique Galibert ◽

Sébastien Corre

Keyword(s):

Cell Lines ◽

Melanoma Cell ◽

Therapeutic Potential ◽

Progression Free Survival ◽

Human Melanoma ◽

Human Melanoma Cell ◽

Melanoma Cell Lines

BRAF and MEK inhibitors (BRAFi and MEKi) are the standard of care for the treatment of metastatic melanoma in patients with BRAFV600E mutations, greatly improving progression-free survival. However, the acquisition of resistance to BRAFi and MEKi remains a difficult clinical challenge, with limited therapeutic options available for these patients. Here, we investigated the therapeutic potential of natural flavonoids as specific AhR (Aryl hydrocarbon Receptor) transcription factor antagonists in combination with BRAFi. Experimental Design: Experiments were performed in vitro and in vivo with various human melanoma cell lines (mutated for BRAFV600E) sensitive or resistant to BRAFi. We evaluated the role of various flavonoids on cell sensitivity to BRAFi and their ability to counteract resistance and the invasive phenotype of melanoma. Results: Flavonoids were highly effective in potentiating BRAFi therapy in human melanoma cell lines by increasing sensitivity and delaying the pool of resistant cells that arise during treatment. As AhR antagonists, flavonoids counteracted a gene expression program associated with the acquisition of resistance and phenotype switching that leads to an invasive and EMT-like phenotype. Conclusions: The use of natural flavonoids opens new therapeutic opportunities for the treatment of patients with BRAF-resistant disease.

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Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated by thrombin in human monocytes and THP-1 cells in vitro and in pregnant subjects in vivo

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613406 ◽

2003 ◽

Vol 89 (06) ◽

pp. 1043-1051 ◽

Cited By ~ 7

Author(s):

Fiona Jordan ◽

Charles Pearson ◽

Isobel D.Walker ◽

Naveed Sattar ◽

Joanne Ellison ◽

...

Keyword(s):

Adhesion Molecule ◽

Activated Protein C ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Fibrinogen Binding ◽

Relationship Of ◽

The Relationship

SummaryMonocytes play a pivotal role in both the inflammatory and coagulation responses, which may be mediated through a variety of adhesion molecules on the cell surface, including intercellular adhesion molecule-1 (ICAM-1). Monocytes also possess thrombin receptors. In the current study, we have demonstrated that thrombin can upregulate ICAM-1 mRNA and induce ICAM-1 expression on the monocyte in vitro and that, in vivo, higher monocyte ICAM-1 expression is observed in pregnancy (which is characterised by a physiological increase in thrombin generation). In pregnant subjects, a positive correlation between monocyte ICAM-1 expression and a number of markers of vascular/thrombotic disease (including blood group, acquired activated protein C resistance and non-fasting plasma triglyceride levels) was observed. We also observed a significant relationship between monocyte ICAM-1 expression and soluble plasma ICAM-1 levels, which would be consistent with a contribution of monocytic ICAM-1 to the levels of free ICAM-1 observed in plasma during pregnancy.Consistent with a role in fibrinogen binding, our preliminary in vivo results suggest that monocyte ICAM-1 expression may be a useful marker of the thrombotic/inflammatory response, although further work is required to assess the relationship of monocyte ICAM-1 expression in thrombotic disorders.

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