The role of CECR1 in the immune-modulatory effects of butyrate and correlation between ADA2 and M1/M2 chemokines in tuberculous pleural effusion

Int Immunopharmacol. 2021 Jul:96:107635. doi: 10.1016/j.intimp.2021.107635. Epub 2021 Apr 12.

Abstract

Objectives: The Cat Eye Syndrome Critical Region, Candidate 1 (CECR1) gene encoding adenosine deaminase 2 (ADA2) is mainly expressed by macrophages. Given the immunomodulatory functions of butyrate, we examined the effect of butyrate on CECR1 expression of macrophages and the relationship between ADA2 and M1/M2 macrophages-associated chemokines in pleural fluid of patients with tuberculous pleural effusion (TPE).

Methods: Expression of CECR1 was evaluated in lipopolysaccharide (LPS)-stimulated and/or butyrate treated THP-1 cells. The role of CECR1 on butyrate-induced immune response was evaluated using siRNA transfected THP-1 cells. M1/M2 chemokines and ADA2 were measured in pleural fluid of patients with TPE.

Results: Butyrate promoted the expression of CECR1 and M2-macrophage markers in THP-1 cells. CECR1 was found to be involved in regulating M2 polarization in THP-1 cells treated with LPS and butyrate. Among chemokines measured in pleural fluid of patients with TPE, there was a significant negative correlation between CCL21 and ADA2 levels and between CCL25 and ADA2 levels, and a significant positive correlation between TGF-β and ADA2 levels and between IL-22 and ADA2 levels.

Conclusions: CECR1 played an important role in the butyrate-modulated inflammatory responses in LPS-stimulated THP-1 cells. ADA2 may exert anti-inflammatory effects during the process of pleural inflammation in patients with TPE.

Keywords: ADA2; Butyrate; CECR1; M2; Tuberculous pleural effusion.

MeSH terms

  • Adenosine Deaminase / genetics*
  • Adenosine Deaminase / immunology*
  • Adenosine Deaminase / metabolism
  • Butyrates / pharmacology*
  • Chemokines / immunology*
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / immunology*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects
  • Macrophages / immunology*
  • Pleural Effusion / immunology*
  • Pleural Effusion / metabolism
  • THP-1 Cells
  • Tuberculosis, Pleural / immunology*

Substances

  • Butyrates
  • Chemokines
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • ADA2 protein, human
  • Adenosine Deaminase