BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a potent cytokine secreted primarily by activated cells from the monocyte/macrophage lineage which exhibits various antitumoral effects including the induction of apoptosis, necrosis, activation of lytic effector cells as well as upregulation of the expression of intercellular adhesion molecule-1 (ICAM-1) which is of decisive importance in the interaction with lymphokine activated killer cells. Previous studies from our laboratory have indicated impaired production of TNF-alpha by monocytes as well as decreased expression of ICAM-1 on monocytes derived from patients with various stages of breast cancer. METHODS: In the present experiments, we have assessed spontaneous as well as lipopolysaccharide (LPS)-induced production of TNF-alpha by as well as expression of ICAM-1 on monocytes derived from healthy females with germline mutations of BRCA1 and from healthy age-matched control females. RESULTS: We report that monocytes derived from healthy women with various germline mutations of BRCA1 had significantly decreased spontaneous (p = 0.03) and LPS-induced (p < 0.001) production of TNF-alpha, as compared to monocytes derived from healthy age-matched control females. In contrast, no difference in LPS- or TNF-alpha-induced production of interleukin-6 was found. Whereas unstimulated monocytes derived from healthy women with germline mutations of BRCA1 and from healthy control women had similar expression of ICAM-1, stimulation with cytokines TNF-alpha and/or interleukin-1 led to a significant increase of ICAM-1 expression on monocytes derived from control females only, but not from BRCA1 germline mutation carriers (p < 0.001). CONCLUSION: We conclude that the presence of germline mutations of BRCA1 was associated with a selective deficiency in spontaneous and LPS-induced production of TNF-alpha and of TNF-alpha-induced ICAM-1 expression on peripheral blood monocytes.
BACKGROUND:Tumour necrosis factor-alpha (TNF-alpha) is a potent cytokine secreted primarily by activated cells from the monocyte/macrophage lineage which exhibits various antitumoral effects including the induction of apoptosis, necrosis, activation of lytic effector cells as well as upregulation of the expression of intercellular adhesion molecule-1 (ICAM-1) which is of decisive importance in the interaction with lymphokine activated killer cells. Previous studies from our laboratory have indicated impaired production of TNF-alpha by monocytes as well as decreased expression of ICAM-1 on monocytes derived from patients with various stages of breast cancer. METHODS: In the present experiments, we have assessed spontaneous as well as lipopolysaccharide (LPS)-induced production of TNF-alpha by as well as expression of ICAM-1 on monocytes derived from healthy females with germline mutations of BRCA1 and from healthy age-matched control females. RESULTS: We report that monocytes derived from healthy women with various germline mutations of BRCA1 had significantly decreased spontaneous (p = 0.03) and LPS-induced (p < 0.001) production of TNF-alpha, as compared to monocytes derived from healthy age-matched control females. In contrast, no difference in LPS- or TNF-alpha-induced production of interleukin-6 was found. Whereas unstimulated monocytes derived from healthy women with germline mutations of BRCA1 and from healthy control women had similar expression of ICAM-1, stimulation with cytokines TNF-alpha and/or interleukin-1 led to a significant increase of ICAM-1 expression on monocytes derived from control females only, but not from BRCA1 germline mutation carriers (p < 0.001). CONCLUSION: We conclude that the presence of germline mutations of BRCA1 was associated with a selective deficiency in spontaneous and LPS-induced production of TNF-alpha and of TNF-alpha-induced ICAM-1 expression on peripheral blood monocytes.
Authors: Ana Custodio; Antonio J López-Farré; José J Zamorano-León; Petra J Mateos-Cáceres; Carlos Macaya; Trinidad Caldés; Miguel de la Hoya; Elena Olivera; Javier Puente; Eduardo Díaz-Rubio; Pedro Pérez-Segura Journal: J Cancer Res Clin Oncol Date: 2012-02-07 Impact factor: 4.553
Authors: Dawit Kidane; Wook Jin Chae; Jennifer Czochor; Kristin A Eckert; Peter M Glazer; Alfred L M Bothwell; Joann B Sweasy Journal: Crit Rev Biochem Mol Biol Date: 2014-01-13 Impact factor: 8.250
Authors: Sara Hägg; Josefin Skogsberg; Jesper Lundström; Peri Noori; Roland Nilsson; Hua Zhong; Shohreh Maleki; Ming-Mei Shang; Björn Brinne; Maria Bradshaw; Vladimir B Bajic; Ann Samnegård; Angela Silveira; Lee M Kaplan; Bruna Gigante; Karin Leander; Ulf de Faire; Stefan Rosfors; Ulf Lockowandt; Jan Liska; Peter Konrad; Rabbe Takolander; Anders Franco-Cereceda; Eric E Schadt; Torbjörn Ivert; Anders Hamsten; Jesper Tegnér; Johan Björkegren Journal: PLoS Genet Date: 2009-12-04 Impact factor: 5.917