Increased secretion of IP-10 from monocytes under hyperglycemia is via the TLR2 and TLR4 pathway

Sridevi Devaraj, Ishwarlal Jialal

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Among the chemokines, members of the CXC family include IP-10 (interferon-gamma induced protein of 10 kDa). Elevated serum IP-10 levels have been shown in diabetes. However, there is a paucity of data examining the sources and regulation of IP-10 under hyperglycemic conditions and this was the overall aim of the study. Type 1 diabetes (T1DM) is a pro-inflammatory state. We previously demonstrated increased toll like receptor (TLR) 2 and 4 activation in monocytes of T1DM patients. Thus, we also examined the role of the TLR pathway in modulating IP-10 release from human monocytes under hyperglycemia. Also, circulating and monocytic levels of IP-10 in patients with T1DM with and without microvascular complications (T1DM-MV and T1DM) and controls (C) was assessed. Under HG, IP-10 mRNA and protein were significantly increased compared to normoglycemia. Incubation of monocytes with dominant negative Ikb but not control vector significantly abrogated HG-induced IP-10 release. Furthermore, both TLR2 siRNA as well as TLR4 siRNA, either alone or in combination significantly abrogated HG-induced IP-10 release. Serum and monocytic levels of IP-10 were significantly increased in T1DM and T1DM-MV compared to matched controls. Thus, we demonstrate increased circulating and monocytic IP-10 in T1DM. Down-regulation of TLR2 and TLR4 abrogates HG-induced IP-10 release via NF-κB inhibition.

Original languageEnglish (US)
Pages (from-to)6-10
Number of pages5
JournalCytokine
Volume47
Issue number1
DOIs
StatePublished - Jul 2009

Keywords

  • Chemokine
  • IP-10
  • Macrophage
  • Toll like receptors
  • Transcription

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

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