Signaling pathways involved in LPS induced TNFalpha production in human adipocytes
| Autor: | Ravi Kumar Murumalla, Frank Tallet, Palaniyandi Ravanan, Maya Cesari, Franck Festy, Pierre Delarue, Karima Bencharif, Laurence Hoareau, Régis Roche, Philippe Rondeau |
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| Přispěvatelé: | Groupe d'Etude sur l'Inflammation Chronique et l'Obésité ( GEICO ), Université de la Réunion ( UR ), CHU Félix Guyon, Groupe d'Etude sur l'Inflammation Chronique et l'Obésité (GEICO), Université de La Réunion (UR), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion] |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Clinical Biochemistry Adipose tissue Inflammation Human Peripheral Blood 03 medical and health sciences Mature Adipocyte 0302 clinical medicine Internal medicine medicine Mononuclear Cell Culture Secretion [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Mononuclear Cell Inflame Adipose Tissue [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology 030304 developmental biology 0303 health sciences business.industry Kinase Research lcsh:RM1-950 Cell Biology Adipose Cell Peripheral Blood Cell biology Cytokine Endocrinology lcsh:Therapeutics. Pharmacology 030220 oncology & carcinogenesis TLR4 Tumor necrosis factor alpha Signal transduction medicine.symptom business |
| Zdroj: | Journal of Inflammation (London, England) Journal of Inflammation Journal of Inflammation, BioMed Central, 2010, 7, pp.1. 〈10.1186/1476-9255-7-1〉 Journal of Inflammation, Vol 7, Iss 1, p 1 (2010) Journal of Inflammation, BioMed Central, 2010, 7, pp.1. ⟨10.1186/1476-9255-7-1⟩ |
| ISSN: | 1476-9255 |
| Popis: | 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 TNFalpha in inflamed adipose tissue, through TLR4 activation. |
| Databáze: | OpenAIRE |
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