Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Signaling pathways involved in LPS induced TNFalpha production in human adipocytes. | Hoareau et al. Journal of Inflammation 2010 7 1 http content 7 1 1 JOURNAL OF INFLAMMATION RESEARCH Open Access Signaling pathways involved in LPS induced TNFalpha production in human adipocytes Laurence Hoareau13 Karima Bencharif13 Philippe Rondeau 1 Ravi Murumalla1 Palaniyandi Ravanan1 Frank Tallet2 Pierre Delarue3 Maya Cesari1 Régis Roche1 3 Franck Festy13 Abstract Background The development of obesity has been linked to an inflammatory process and the role of adipose tissue in the secretion of pro-inflammatory molecules such as IL-6 or TNFalpha has now been largely confirmed. Although TNFalpha secretion by adipose cells is probably induced most notably by TLR ligands the activation and secretion pathways of this cytokine are not yet entirely understood. Moreover given that macrophagic infiltration is a characteristic of obesity it is difficult to clearly establish the level of involvement of the different cellular types present within the adipose tissue during inflammation. Methods Primary cultures of human adipocytes and human peripheral blood mononuclear cells were used. Cells were treated with a pathogen-associated molecular pattern LPS with and without several kinase inhibitors. Western blot for p38 MAP Kinase was performed on cell lysates. TNFalpha mRNA was detected in cells by RT-PCR and TNFalpha protein was detected in supernatants by ELISA assays. Results We show for the first time that the production of TNFalpha in mature human adipocytes is mainly dependent upon two pathways NFkappaB and p38 MAP Kinase. Moreover we demonstrate that the PI3Kinase pathway is clearly involved in the first step of the LPS-pathway. Lastly we show that adipocytes are able to secrete a large amount of TNFalpha compared to macrophages. Conclusion This study clearly demonstrates that the LPS induced activation pathway is an integral part of the inflammatory process linked to obesity and that adipocytes are responsible for most of the secreted .
