Oral squamous carcinoma cells promote macrophage polarization in an MIF-dependent manner.

BACKGROUND: Tumor-associated macrophages (TAMs) are important determinants of intratumoral immune evasion, neoangiogenesis, extracellular matrix remodeling and dysregulated tumor cell proliferation. Our prior studies revealed that macrophage-derived, but not tumor cell-derived, macrophage migration inhibitory factor (MIF), is an important determinant of TAM alternative activation and M2 polarization. AIM: Because MIF is historically thought to initiate signaling via a receptor-dependent, outside-in mode of action, we wished to investigate the specific contributions of tumor-derived vs. macrophage-derived MIF to M2 marker expression during macrophage polarization. DESIGN: Murine oral squamous cell-carcinoma cells (SCCVII) were co-cultured with either the RAW 264.7 mouse macrophage cell line or mouse primary bone marrow-derived macrophages in the context of MIF genetic loss/inhibition individually or in combination each cell type. METHODS: Twelve well Transwell plates were used to co-culture SCCVII cells and RAW 264.7, MIF+/+ or MIF-/- macrophages treated with/without the small molecule MIF inhibitor, 4-iodo-6-phenylpyrimidine and incubated in the presence or absence of interleukin (IL-4) for 48 h. Macrophages were analyzed by quantitative real-time polymerase chain reaction and/or immunoblotting for relative macrophage polarization marker expression. RESULTS: IL-4 treatment synergizes with SCCVII co-culture in inducing the expression of macrophage M2 markers and loss or inhibition of macrophage-derived MIF significantly reduces both IL-4 alone and IL-4/SCCVII co-culture-induced macrophage M2 marker expression. CONCLUSION: These studies identify an important and dominant requirement for macrophage MIF in maximal Th2-cytokine and oral squamous carcinoma cell-induced macrophage polarization and M2 marker expression.

Development and characterization of starch nanoparticles by gamma radiation: potential application as starch matrix filler.

Gamma radiation arises as an advantageous alternative to obtain starch nanoparticles given its low cost, simple methodology and scalability. Starch nanoparticles (SNP) with sizes around 20 and 30 nm were obtained applying a dose of 20 kGy from cassava (CNP-γ) and waxy maize (WNP-γ) starch, respectively. They showed the same thermal degradation behavior and their maximum mass loss zone was similar to those nanoparticles obtained from acid hydrolysis (WNP-h). Additionally, CNP-γ and WNP-γ were used as nanofillers in a cassava matrix. Increments of 102% in storage modulus were obtained with the addition of only 2.5 wt.% of WNP-γ, showing that gamma radiation is a successful methodology to obtain SNP able to be used as starch reinforcement.