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

Zsolt Sarang, Krisztina Köröskényi, Anna Pallai, Edina Duró, Gerry Melino, Martin Griffin, László Fésüs, Zsuzsa Szondy

Research output: Contribution to journalArticle

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 ß(3) coreceptor in the engulfment process, while altered proinflammatory cytokine production is related to the lack of latent TGFß activation by TG2 null macrophages. Here we report that TG2 null macrophages respond to lipopolysaccharide treatment by elevated IL-6 and TNFa production. Though TGFß 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 TGFß production. Instead, in the absence of TG2 integrin ß(3) maintains an elevated basal Src family kinase activity in macrophages, which leads to enhanced phosphorylation and degradation of the I?Ba. Low basal levels of I?Ba explain the enhanced sensitivity of TG2 null macrophages to signals that regulate NF-?B. 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
Early online date21 Mar 2011
DOIs
Publication statusPublished - Jul 2011

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

Bibliographical note

© 2011, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • immunologic adjuvants
  • animals
  • cytokines
  • GTP-binding proteins
  • I-kappa B proteins
  • integrin alphaVbeta3
  • lipopolysaccharides
  • macrophages
  • mice
  • inbred C57BL mice
  • knockout mice
  • NF-kappa B
  • signal transduction
  • transforming growth factor beta
  • transglutaminases
  • src-family kinases

Cite this

Sarang, Zsolt ; Köröskényi, Krisztina ; Pallai, Anna ; Duró, Edina ; Melino, Gerry ; Griffin, Martin ; Fésüs, László ; Szondy, Zsuzsa. / Transglutaminase 2 null macrophages respond to lipopolysaccharide stimulation by elevated proinflammatory cytokine production due to an enhanced αvβ3 integrin-induced Src tyrosine kinase signaling. In: Immunology Letters. 2011 ; Vol. 138, No. 1. pp. 71-78.
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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, Zsolt; Köröskényi, Krisztina; Pallai, Anna; Duró, Edina; Melino, Gerry; Griffin, Martin; Fésüs, László; Szondy, Zsuzsa.

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

Research output: Contribution to journalArticle

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AU - Duró, Edina

AU - Melino, Gerry

AU - Griffin, Martin

AU - Fésüs, László

AU - Szondy, Zsuzsa

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