Transforming growth factor β-induced protein promotes severe vascular inflammatory responses

Jong Sup Bae, Wonhwa Lee, Ju Ock Nam, Jung Eun Kim, Shin Woo Kim, In San Kim

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Rationale: Sepsis is a systemic inflammatory condition resulting from bacterial infections; it has a high mortality rate and limited therapeutic options. Despite extensive research into the mechanisms driving bacterial sepsis, the target molecules controlling vascular leakage are still largely unknown. Transforming growth factor b-induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types, which is known to interact with integrins. Objectives: The aim of this study was to determine the roles of TGFBIp in vascular proinflammatory responses, and the mechanisms of action driving these responses. Methods: Circulating levels of TGFBIp were measured in patients admitted to the hospital with sepsis, severe sepsis, and septic shock and in cecal ligation and puncture (CLP)-induced septic mice. Effects of TGFBIp knockout on CLP-induced septic mortality and effects of TGFBIp on multiple vascular proinflammatory responses were determined. Measurements and Main Results: Circulating levels of TGFBIp were significantly elevated compared with healthy controls, and were strongly correlated with disease severity. High blood TGFBIp levels were also observed in CLP-induced septic mice. The absence of the TGFBIp gene in mice attenuated CLP-induced sepsis. TGFBIp enhanced vascular proinflammatory responses including vascular permeability, adhesion and migration of leukocytes, and disruption of adherence junctions through interacting with integrin avb5. Conclusions: Collectively, our findings demonstrate that the TGFBIp-avb5 axis can elicit severe inflammatory responses, suggesting it to be a potential target for development of diagnostics and therapeutics for sepsis.

Original languageEnglish
Pages (from-to)779-786
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume189
Issue number7
DOIs
Publication statusPublished - 2014 Apr 1

Keywords

  • Cecal ligation and puncture
  • Endothelial dysfunction
  • Permeability
  • Sepsis
  • Transforming growth factor b-induced protein

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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