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. Mechanisms linking the metabolic syndrome and cardiovascular disease: role of hepatic insulin resistance. J Teh Univ Heart Ctr. 2009;2:77–84.
- Kenner KA, Anyanwu E, Olefsky JM, Kusari J. Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor I-stimulated signaling. J Biol Chem. 1996;271:19810–6. CrossRef
- Buckley DA, Cheng A, Kiely PA, Tremblay ML, O’Connor R. 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. 2002;22:1998–2010. CrossRef
- Heinonen KM, Dube N, Bourdeau A, Lapp WS, Tremblay ML. Protein tyrosine phosphatase 1B negatively regulates macrophage development through CSF-1 signaling. Proc Natl Acad Sci USA. 2006;103:2776–81. CrossRef
- Flint AJ, Tiganis T, Barford D, Tonks NK. Development of “substrate-trapping” mutants to identify physiological substrates of protein tyrosine phosphatases. Proc Natl Acad Sci USA. 1997;94:1680–5. CrossRef
- Haj FG, Verveer PJ, Squire A, Neel BG, Bastiaens PI. Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science. 2002;295:1708–11. 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. Increased abundance of specific skeletal muscle protein-tyrosine phosphatases in a genetic model of insulin-resistant obesity and diabetes mellitus. Metabolism. 1995;44:1175–84. CrossRef
- Dadke SS, Li HC, Kusari AB, Begum N, Kusari J. 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. 2000;274:583–9. CrossRef
- Zabolotny JM, Kim YB, Welsh LA, Kershaw EE, Neel BG, Kahn BB. Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. J Biol Chem. 2008;283:14230–41. CrossRef
- Parvaneh L, Meshkani R, Bakhtiyari S, Mohammadtaghvaie N, Gorganifiruzjaee S, Taheripak G, Golestani A, Foruzandeh M, Larijani B, Taghikhani M. Palmitate and inflammatory state additively induce the expression of PTP1B in muscle cells. Biochem Biophys Res Commun. 2010;396:467–71. CrossRef
- MohammadTaghvaei N, Meshkani R, Taghikhani M, Larijani B, Adeli K. Palmitate enhances protein tyrosine phosphatase 1B (PTP1B) gene expression at transcriptional level in C2C12 skeletal muscle cells. Inflammation. 2011;34:43–8. CrossRef
- Inada S, Ikeda Y, Suehiro T, Takata H, Osaki F, Arii K, Kumon Y, Hashimoto K. Glucose enhances protein tyrosine phosphatase 1B gene transcription in hepatocytes. Mol Cell Endocrinol. 2007;271:64–70. CrossRef
- Bourdeau A, Dubé N, Tremblay ML. Cytoplasmic protein tyrosine phosphatases, regulation and function: the roles of PTP1B and TC-PTP. Curr Opin Cell Biol. 2005;17:203–9. CrossRef
- Myers MP, Andersen JN, Cheng A, Tremblay ML, Horvath CM, Parisien JP, Salmeen A, Barford D, Tonks NK. TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. J Biol Chem. 2001;276:47771–4. CrossRef
- Xu H, An H, Hou J, Han C, Wang P, Yu Y, Cao X. Phosphatase PTP1B negatively regulates MyD88- and TRIF-dependent proinflammatory cytokine and type I interferon production in TLR-triggered macrophages. Mol Immunol. 2008;45:3545–52. CrossRef
- Heinonen KM, Bourdeau A, Doody KM, Tremblay ML. Protein tyrosine phosphatases PTP-1B and TC-PTP play nonredundant roles in macrophage development and IFN-gamma signaling. Proc Natl Acad Sci USA. 2009;106:9368–72. CrossRef
- Berdnikovs S, Pavlov VI, Abdala-Valencia H, McCary CA, Klumpp DJ, Tremblay ML, Cook-Mills JM. PTP1B deficiency exacerbates inflammation and accelerates leukocyte trafficking in vivo. J Immunol. 2012;188:874–84. 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. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Invest. 2011;121:1858–70. CrossRef
- Dasu MR, Jialal I. Free fatty acids in the presence of high glucose amplify monocyte inflammation via Toll-like receptors. Am J Physiol Endocrinol Metab. 2011;300:E145–54. CrossRef
- Bakhtiyari S, Meshkani R, Taghikhani M, Larijani B, Adeli K. Protein tyrosine phosphatase-1B (PTP-1B) knockdown improves palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Lipids. 2010;45:237–44. CrossRef
- Meshkani R, Adeli K, Meshkani R, Adeli K. Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clin Biochem. 2009;42:1331–46. CrossRef
- Nguyen MT, Favelyukis S, Nguyen AK, Reichart D, Scott PA, Jenn A, Liu-Bryan R, Glass CK, Neels JG, Olefsky JM. 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. 2007;282(48):35279–92. CrossRef
- Samokhvalov V, Bilan PJ, Schertzer JD, Antonescu CN, Klip A. Palmitate- and lipopolysaccharide-activated macrophages evoke contrasting insulin responses in muscle cells. Am J Physiol Endocrinol Metab. 2009;296:E37–46. 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. Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress. J Biol Chem. 2004;279:49689–93. CrossRef
- Sangwan V, Paliouras GN, Cheng A, Dubé N, Tremblay ML, Park M. Protein-tyrosine phosphatase 1B deficiency protects against Fas-induced hepatic failure. J Biol Chem. 2006;281:221–8. CrossRef
- González-Rodriguez A, Escribano O, Alba J, Rondinone CM, Benito M, Valverde AM. Levels of protein tyrosine phosphatase 1B determine susceptibility to apoptosis in serum-deprived hepatocytes. J Cell Physiol. 2007;212:76–88. 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. 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. 2007;27:84–91. CrossRef
- Schwartz EA, Zhang WY, Karnik SK, Borwege S, Anand VR, Laine PS, Su Y, Reaven PD. Nutrient modification of the innate immune response: a novel mechanism by which saturated fatty acids greatly amplify monocyte inflammation. Arterioscler Thromb Vasc Biol. 2010;30:802–8. 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