We investigated the effects of zinc deficiency on acute lung injury （ALI） induced by mechanical ventilation. Male Sprague-Dawley rats were fed with a zinc-deficient or zinc-proficient diet for 4 weeks, and then rece...We investigated the effects of zinc deficiency on acute lung injury （ALI） induced by mechanical ventilation. Male Sprague-Dawley rats were fed with a zinc-deficient or zinc-proficient diet for 4 weeks, and then received mechanical ventilation at normal frequency and pressure for 30 min. Total protein, cell count, the number of poly- morphonuclear neutrophil （PMN） in the bronchoalveolar lavage （BAL）, and vascular endothelial growth factor （VEGF） expression in the lung were determined. Activation of nuclear factor-t^B （NF-~cB） was detected by exam- ining the phosphorylation of NF-kB （pNF-kB p65） and the expression of inhibitor of NF-kB （pI-kBa）. Compared to the controls, total cell count and the number of PMNs were significantly increased to 160% and 140%, respec- tively, in zinc-deficient rats treated with ventilation. Activation of NF-kB was significantly increased and VEGF was also increased to three-folds. Zinc deficiency aggravated the inflammatory response in rats and was associated with the overexpression of VEGF in response to mechanical ventilation. Zinc supplementation may be beneficial to zinc-deficient patients during mechanical ventilation.展开更多
Tumor-associated macrophages （TAMs） play a critical role in melanoma growth and metastasis. Infiltration of TAMs correlates with the poor prognosis of melanoma. TAMs are differentiated from monocytes in response to ...Tumor-associated macrophages （TAMs） play a critical role in melanoma growth and metastasis. Infiltration of TAMs correlates with the poor prognosis of melanoma. TAMs are differentiated from monocytes in response to the tumor microenvironment cue. However, the mechanism how TAMs adapt to the tumor microenvironment after differentiation from monocytes is not fully understood. In addition, specific identification of TAMs in melanoma is difficult because the expression of the most commonly used macrophage marker, CD68, is also expressed in melanoma cells. In an earlier study, we found by gene microarray analysis that seven members of the metallothionein （MTs） family were upregulated in melanoma-conditioned medium induced macrophages （MCIM-MO）. MTs have been implicated in zinc metabolism and inflammation. In the present study, we confirmed that expression of metallothionein is induced in M-CSF differentiated macrophages （M-CSF/M~） and MCIM-M~ at both the mRNA and protein levels using real-time PCR, immunofluorescence, and western blot analysis. Furthermore, we demonstrated the presence of metallothionein in melanoma tissues in vivo and that metallothionein was co-localized with TAMs markers, CD68 and CD163. Finally, we demonstrated the induction of the zinc importer gene Zip8 both in M-CSF/MO and MCIM-MO. Our study identifies metallothionein as a novel marker for TAMs and suggests that metaliothionein might play important roles in macrophage adaptation and function in the tumor microenvironment.展开更多
文摘We investigated the effects of zinc deficiency on acute lung injury （ALI） induced by mechanical ventilation. Male Sprague-Dawley rats were fed with a zinc-deficient or zinc-proficient diet for 4 weeks, and then received mechanical ventilation at normal frequency and pressure for 30 min. Total protein, cell count, the number of poly- morphonuclear neutrophil （PMN） in the bronchoalveolar lavage （BAL）, and vascular endothelial growth factor （VEGF） expression in the lung were determined. Activation of nuclear factor-t^B （NF-~cB） was detected by exam- ining the phosphorylation of NF-kB （pNF-kB p65） and the expression of inhibitor of NF-kB （pI-kBa）. Compared to the controls, total cell count and the number of PMNs were significantly increased to 160% and 140%, respec- tively, in zinc-deficient rats treated with ventilation. Activation of NF-kB was significantly increased and VEGF was also increased to three-folds. Zinc deficiency aggravated the inflammatory response in rats and was associated with the overexpression of VEGF in response to mechanical ventilation. Zinc supplementation may be beneficial to zinc-deficient patients during mechanical ventilation.
文摘Tumor-associated macrophages （TAMs） play a critical role in melanoma growth and metastasis. Infiltration of TAMs correlates with the poor prognosis of melanoma. TAMs are differentiated from monocytes in response to the tumor microenvironment cue. However, the mechanism how TAMs adapt to the tumor microenvironment after differentiation from monocytes is not fully understood. In addition, specific identification of TAMs in melanoma is difficult because the expression of the most commonly used macrophage marker, CD68, is also expressed in melanoma cells. In an earlier study, we found by gene microarray analysis that seven members of the metallothionein （MTs） family were upregulated in melanoma-conditioned medium induced macrophages （MCIM-MO）. MTs have been implicated in zinc metabolism and inflammation. In the present study, we confirmed that expression of metallothionein is induced in M-CSF differentiated macrophages （M-CSF/M~） and MCIM-M~ at both the mRNA and protein levels using real-time PCR, immunofluorescence, and western blot analysis. Furthermore, we demonstrated the presence of metallothionein in melanoma tissues in vivo and that metallothionein was co-localized with TAMs markers, CD68 and CD163. Finally, we demonstrated the induction of the zinc importer gene Zip8 both in M-CSF/MO and MCIM-MO. Our study identifies metallothionein as a novel marker for TAMs and suggests that metaliothionein might play important roles in macrophage adaptation and function in the tumor microenvironment.
