Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.     

Potential roles of chromium on inflammatory biomarkers in diabetes: A Systematic

Diabetes, as a low‐grade chronic inflammatory disease, causes disruption in proper function of immune and metabolic system. Chromium is an important element required for normal lipid and glucose metabolism. Chromium deficiency is correlated with elevation in cardiometabolic risk, which results from increased inflammation. This systematic review was conducted to discover the potential roles of chromium on inflammatory biomarkers. Eligible studies were all in vitro, animal and human studies published in English‐language journals from inception until October 2018. PubMed, Scopus, Embase, ProQuest and Google Scholar databases were searched to fined interventional studies from the effects of chromium on inflammatory biomarkers such as tumour necrosis factor a (TNF‐a), C‐reactive protein (CRP), interleukins, monocyte chemoattractant protein–1 (MCP‐1), intercellular adhesion molecule‐1 (ICAM‐1) and adipocytokines in hyperglycaemia and diabetes. Out of 647 articles found in the search, only 14 articles were eligible for analysis, three in vitro studies, eight animal studies and three human studies. Twelve of the 14 studies included in this review, chromium significantly decreased inflammatory factors. The findings of this review indicate, based on in vitro and in vivo studies, that chromium might have potential anti‐inflammatory properties, but some of the studies did not show anti‐inflammatory effects for chromium (two studies). There are only three studies in humans with controversial results. Therefore, more consistent randomized double‐blind controlled trials are needed to reach relevant clinical recommendations, as well as to determine the precise mechanism, of chromium on inflammation in diabetes.