C57BL/6N Mice Are More Resistant to Ehrlich Ascites Tumors Than C57BL/6J Mice: The Role of Macrophage Nitric Oxide

Abstract

BackgroundEffectiveness of the immune defense formed by the genotype often determines the predisposition to cancer. Nitric oxide (NO) produced by macrophages is an important element in this defense.Material/MethodsWe hypothesized that genetic characteristics of NO generation systems can predetermine the vulnerability to tumor development. The study was conducted on mice of 2 genetic substrains – C57BL/6J and C57BL/6N – with Ehrlich ascites carcinoma (EAC). NO production in the tumor was changed using ITU, an iNOS inhibitor; c-PTIO, a NO scavenger; and SNP, a NO donor. Macrophage NO production was estimated by nitrite concentration in the culture medium. iNOS content was measured by Western blot analysis. Macrophage phenotype was determined by changes in NO production, iNOS level, and CD markers of the phenotype.ResultsThe lifespan of C57BL/6N mice (n=10) with EAC was 25% longer (p<0.01) than in C57BL/6J mice (n=10). Decreased NO production 23% reduced the survival duration of C57BL/6N mice (p<0.05), which were more resistant to tumors. Elevated NO production 26% increased the survival duration of C57BL/6J mice (p<0.05), which were more susceptible to EAC. Both the NO production and the iNOS level were 1.5 times higher in C57BL/6N than in C57BL/6J mice (p<0.01). CD markers confirmed that C57BL/6N macrophages had the M1 and C57BL/6J macrophages had the M2 phenotype.ConclusionsThe vulnerability to the tumor development can be predetermined by genetic characteristics of the NO generation system in macrophages. The important role of NO in anti-EAC immunity should be taken into account in elaboration of new antitumor therapies.

RETRACTED: NOSH-NBP, a Novel Nitric Oxide and Hydrogen Sulfide- Releasing Hybrid, Attenuates Ischemic Stroke-Induced Neuroinflammatory Injury by Modulating Microglia Polarization

“…From a physiological perspective, although NO and H 2 S have some similar functions, such as blood vessel relaxation, they act on different downstream targets, including respectively soluble guanylyl cyclase/cyclic guanosine monophosphate (sGC-cGMP) and the potassium (K + ) channel (Mustafa et al, 2009). In peripheral macrophages, the expression of CD206, a M2 marker, is insensitive to the change of endogenous NO content, whereas elevation of H 2 S production by CBS overexpression not only inhibits M1 markers but also promotes M2 markers (Chao et al, 2015; Kalish et al, 2015). These observations provide the possible differences between NO and H 2 S in the regulation of microglial polarization.…”

A combination of genetics and microbiota influences the severity of the obesity phenotype in diet-induced obesity

“…Several studies reported an increased proinflammatory response in B6N mice compared to that in B6J mice 10,20 . Macrophages from B6N mice displayed a more activated M1 phenotype and produced more NO than those from B6J mice in a tumor model 19 . Obesity is often described as a chronic state of low-grade inflammation 16,17,48 .…”

“…Immunological differences between B6 substrains have been described previously. B6N mice exhibited a more activated and proinflammatory phenotype than B6J mice 10,19,20 . However, immunological differences among the substrains under conditions of obesity need to be further analyzed.…”

Avaliação farmacológica sinérgica do composto monofosfoester 2-AEH2F associado com fármacos envolvidos no metabolismo tumoral no modelo de carcinomatose de mama de Ehrlich

“…O tumor de Ehrlich é considerado uma neoplasia transplantável que tem origem epitelial maligna, que corresponde ao adenocarcinoma mamário de camundongos fêmeas 41 , 42 . Caracteriza-se como um modelo que prolifera rapidamente possuindo células pleomórficas e anaplásicas as quais apresentam relação núcleo citoplasma, nucléolos múltiplos e proeminentes, além do núcleo com a cromatina frouxa 43 .…”