Transglutaminase 2 null macrophages respond to lipopolysaccharide stimulation by elevated proinflammatory cytokine production due to an enhanced αvβ3 integrin-induced Src tyrosine kinase signaling

Z. Sarang, Krisztina Köröskényi, Anna Pallai, Edina Duró, Gerry Melino, Martin Griffin, L. Fésüs, Z. Szondy

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Transglutaminase 2 (TG2) is a protein crosslinking enzyme with several additional biochemical functions. Loss of TG2 in vivo results in impaired phagocytosis of apoptotic cells and altered proinflammatory cytokine production by macrophages engulfing apoptotic cells leading to autoimmunity. It has been proposed that TG2 acts as an integrin β3 coreceptor in the engulfment process, while altered proinflammatory cytokine production is related to the lack of latent TGFβ activation by TG2 null macrophages. Here we report that TG2 null macrophages respond to lipopolysaccharide treatment by elevated IL-6 and TNFα production. Though TGFβ has been proposed to act as a feed back regulator of proinflammatory cytokine production in LPS-stimulated macrophages, this phenomenon is not related to the lack of active TGFβ production. Instead, in the absence of TG2 integrin β3 maintains an elevated basal Src family kinase activity in macrophages, which leads to enhanced phosphorylation and degradation of the IκBα. Low basal levels of IκBα explain the enhanced sensitivity of TG2 null macrophages to signals that regulate NF-κB. Our data suggest that TG2 null macrophages bear a proinflammatory phenotype, which might contribute to the enhanced susceptibility of these mice to develop autoimmunity and atherosclerosis.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalImmunology Letters
Volume138
Issue number1
DOIs
Publication statusPublished - Jul 2011

Fingerprint

src-Family Kinases
Integrins
Lipopolysaccharides
Macrophages
Cytokines
Autoimmunity
Cytophagocytosis
transglutaminase 2
Interleukin-6
Atherosclerosis
Phosphorylation
Phenotype
Enzymes

Keywords

  • Inflammation
  • Macrophages
  • NF-kB pathway
  • TGF-beta
  • Toll like receptors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Transglutaminase 2 null macrophages respond to lipopolysaccharide stimulation by elevated proinflammatory cytokine production due to an enhanced αvβ3 integrin-induced Src tyrosine kinase signaling. / Sarang, Z.; Köröskényi, Krisztina; Pallai, Anna; Duró, Edina; Melino, Gerry; Griffin, Martin; Fésüs, L.; Szondy, Z.

In: Immunology Letters, Vol. 138, No. 1, 07.2011, p. 71-78.

Research output: Contribution to journalArticle

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