Protein tyrosine phosphatase 1B (PTP1B) modulates palmitate-induced cytokine production in macrophage cells
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
The aim of the study was to investigate the effect of PTP1B modulation on palmitate-induced cytokine production in macrophages.
Lentiviruses carrying PTP1B-shRNA or cDNA at different multiplicities of infection (MOIs) were used to decrease and increase PTP1B expression in Raw 264.7 cells, respectively. mRNA and protein levels of TNF-α and IL-6 were measured by real-time PCR and ELISA, respectively.
0.5 mM palmitate reduced PTP1B mRNA and protein levels by 25 and 19 %, respectively, compared to untreated cells. Overexpression of PTP1B decreased mRNA and protein levels of TNF-α and IL-6 in macrophages stimulated with palmitate. We found that protein and mRNA levels of cytokines significantly increased in knockdown cells stimulated by palmitate in a dose-dependent manner with increased MOI. NF-kB, JNK, p38 and ERK specific inhibitors significantly reduced the production of TNF-α and IL-6 in macrophages stimulated with palmitate and also PTP1B knockdown cells. Furthermore, inhibition of PTP1B resulted in increased phosphorylation of JNK, p38, ERK and NF-kB p65 in macrophage cells.
The data of this study demonstrate that PTP1B negatively regulates palmitate-induced cytokine secretion in macrophages by mechanisms involving the activation of MAPKs and NF-kB pathways.
- Meshkani, R, Adeli, K (2009) Mechanisms linking the metabolic syndrome and cardiovascular disease: role of hepatic insulin resistance. J Teh Univ Heart Ctr 2: pp. 77-84
- Kenner, KA, Anyanwu, E, Olefsky, JM, Kusari, J (1996) Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor I-stimulated signaling. J Biol Chem 271: pp. 19810-19816 CrossRef
- Buckley, DA, Cheng, A, Kiely, PA, Tremblay, ML, O’Connor, R (2002) Regulation of insulin-like growth factor type I (IGF-I) receptor kinase activity by protein tyrosine phosphatase 1B (PTP-1B) and enhanced IGF-I-mediated suppression of apoptosis and motility in PTP1B deficient fibroblasts. Mol Cell Biol 22: pp. 1998-2010 CrossRef
- Heinonen, KM, Dube, N, Bourdeau, A, Lapp, WS, Tremblay, ML (2006) Protein tyrosine phosphatase 1B negatively regulates macrophage development through CSF-1 signaling. Proc Natl Acad Sci USA 103: pp. 2776-2781 CrossRef
- Flint, AJ, Tiganis, T, Barford, D, Tonks, NK (1997) Development of “substrate-trapping” mutants to identify physiological substrates of protein tyrosine phosphatases. Proc Natl Acad Sci USA 94: pp. 1680-1685 CrossRef
- Haj, FG, Verveer, PJ, Squire, A, Neel, BG, Bastiaens, PI (2002) Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science 295: pp. 1708-1711 CrossRef
- Shi K, Egawa K, Maegawa H, Nakamura T, Ugi S, Nishio Y, Kashiwagi A. Protein-tyrosine phosphatase 1B associates with insulin receptor and negatively regulates insulin signaling without receptor internalization. J. Biochem. 2004;136:89–96.
- Ahmad, F, Goldstein, BJ (1995) Increased abundance of specific skeletal muscle protein-tyrosine phosphatases in a genetic model of insulin-resistant obesity and diabetes mellitus. Metabolism 44: pp. 1175-1184 CrossRef
- Dadke, SS, Li, HC, Kusari, AB, Begum, N, Kusari, J (2000) Elevated expression and activity of protein-tyrosine phosphatase 1B in skeletal muscle of insulin-resistant type II diabetic Goto–Kakizaki rats. Biochem Biophys Res Commun 274: pp. 583-589 CrossRef
- Zabolotny, JM, Kim, YB, Welsh, LA, Kershaw, EE, Neel, BG, Kahn, BB (2008) Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. J Biol Chem 283: pp. 14230-14241 CrossRef
- Parvaneh, L, Meshkani, R, Bakhtiyari, S, Mohammadtaghvaie, N, Gorganifiruzjaee, S, Taheripak, G, Golestani, A, Foruzandeh, M, Larijani, B, Taghikhani, M (2010) Palmitate and inflammatory state additively induce the expression of PTP1B in muscle cells. Biochem Biophys Res Commun 396: pp. 467-471 CrossRef
- MohammadTaghvaei, N, Meshkani, R, Taghikhani, M, Larijani, B, Adeli, K (2011) Palmitate enhances protein tyrosine phosphatase 1B (PTP1B) gene expression at transcriptional level in C2C12 skeletal muscle cells. Inflammation 34: pp. 43-48 CrossRef
- Inada, S, Ikeda, Y, Suehiro, T, Takata, H, Osaki, F, Arii, K, Kumon, Y, Hashimoto, K (2007) Glucose enhances protein tyrosine phosphatase 1B gene transcription in hepatocytes. Mol Cell Endocrinol 271: pp. 64-70 CrossRef
- Bourdeau, A, Dubé, N, Tremblay, ML (2005) Cytoplasmic protein tyrosine phosphatases, regulation and function: the roles of PTP1B and TC-PTP. Curr Opin Cell Biol 17: pp. 203-209 CrossRef
- Myers, MP, Andersen, JN, Cheng, A, Tremblay, ML, Horvath, CM, Parisien, JP, Salmeen, A, Barford, D, Tonks, NK (2001) TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. J Biol Chem 276: pp. 47771-47774 CrossRef
- Xu, H, An, H, Hou, J, Han, C, Wang, P, Yu, Y, Cao, X (2008) Phosphatase PTP1B negatively regulates MyD88- and TRIF-dependent proinflammatory cytokine and type I interferon production in TLR-triggered macrophages. Mol Immunol 45: pp. 3545-3552 CrossRef
- Heinonen, KM, Bourdeau, A, Doody, KM, Tremblay, ML (2009) Protein tyrosine phosphatases PTP-1B and TC-PTP play nonredundant roles in macrophage development and IFN-gamma signaling. Proc Natl Acad Sci USA 106: pp. 9368-9372 CrossRef
- Berdnikovs, S, Pavlov, VI, Abdala-Valencia, H, McCary, CA, Klumpp, DJ, Tremblay, ML, Cook-Mills, JM (2012) PTP1B deficiency exacerbates inflammation and accelerates leukocyte trafficking in vivo. J Immunol 188: pp. 874-884 CrossRef
- Holland, WL, Bikman, BT, Wang, LP, Yuguang, G, Sargent, KM, Bulchand, S, Knotts, TA, Shui, G, Clegg, DJ, Wenk, MR, Pagliassotti, MJ, Scherer, PE, Summers, SA (2011) Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Invest 121: pp. 1858-1870 CrossRef
- Dasu, MR, Jialal, I (2011) Free fatty acids in the presence of high glucose amplify monocyte inflammation via Toll-like receptors. Am J Physiol Endocrinol Metab 300: pp. E145-E154 CrossRef
- Bakhtiyari, S, Meshkani, R, Taghikhani, M, Larijani, B, Adeli, K (2010) Protein tyrosine phosphatase-1B (PTP-1B) knockdown improves palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Lipids 45: pp. 237-244 CrossRef
- Meshkani, R, Adeli, K, Meshkani, R, Adeli, K (2009) Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clin Biochem 42: pp. 1331-1346 CrossRef
- Nguyen, MT, Favelyukis, S, Nguyen, AK, Reichart, D, Scott, PA, Jenn, A, Liu-Bryan, R, Glass, CK, Neels, JG, Olefsky, JM (2007) A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 282: pp. 35279-35292 CrossRef
- Samokhvalov, V, Bilan, PJ, Schertzer, JD, Antonescu, CN, Klip, A (2009) Palmitate- and lipopolysaccharide-activated macrophages evoke contrasting insulin responses in muscle cells. Am J Physiol Endocrinol Metab 296: pp. E37-E46 CrossRef
- MohammadTaghvaei N, Taheripak G, Taghikhani M, Meshkani R. Palmitate-induced PTP1B expression is mediated by ceramide-JNK and nuclear factor κB (NF-κB) activation. Cell Signal. 2012;24(10):1964–70.
- Gu, F, Nguyên, DT, Stuible, M, Dubé, N, Tremblay, ML, Chevet, E (2004) Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress. J Biol Chem 279: pp. 49689-49693 CrossRef
- Sangwan, V, Paliouras, GN, Cheng, A, Dubé, N, Tremblay, ML, Park, M (2006) Protein-tyrosine phosphatase 1B deficiency protects against Fas-induced hepatic failure. J Biol Chem 281: pp. 221-228 CrossRef
- González-Rodriguez, A, Escribano, O, Alba, J, Rondinone, CM, Benito, M, Valverde, AM (2007) Levels of protein tyrosine phosphatase 1B determine susceptibility to apoptosis in serum-deprived hepatocytes. J Cell Physiol 212: pp. 76-88 CrossRef
- Suganami, T, Tanimoto-Koyama, K, Nishida, J, Itoh, M, Yuan, X, Mizuarai, S, Kotani, H, Yamaoka, S, Miyake, K, Aoe, S, Kamei, Y, Ogawa, Y (2007) Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 27: pp. 84-91 CrossRef
- Schwartz, EA, Zhang, WY, Karnik, SK, Borwege, S, Anand, VR, Laine, PS, Su, Y, Reaven, PD (2010) Nutrient modification of the innate immune response: a novel mechanism by which saturated fatty acids greatly amplify monocyte inflammation. Arterioscler Thromb Vasc Biol 30: pp. 802-808 CrossRef
- Protein tyrosine phosphatase 1B (PTP1B) modulates palmitate-induced cytokine production in macrophage cells
Volume 62, Issue 2 , pp 239-246
- Cover Date
- Print ISSN
- Online ISSN
- SP Birkhäuser Verlag Basel
- Additional Links
- Protein tyrosine phosphatase 1B (PTP1B)
- Industry Sectors