title: Protein tyrosine phosphatase 1B (PTP1B) modulates palmitate-induced cytokine production in macrophage cells.
abstract: OBJECTIVE
  The aim of the study was to investigate the effect of PTP1B modulation on palmitate-induced cytokine production in macrophages.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Nasimian
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Taheripak
authors.forename: Sattar
authors.initials: S
authors.lastname: Gorgani-Firuzjaee
authors.forename: Asie
authors.initials: A
authors.lastname: Sadeghi
authors.forename: Reza
authors.initials: R
authors.lastname: Meshkani
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010168:Palmitates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D010168:Palmitates; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse