Clostridium difficile toxins or infection induce upregulation of adenosine receptors and IL-6 with early pro-inflammatory and late anti-inflammatory pattern

• Published in: Brazilian journal of medical and biological research Vol. 53; no. 9; pp. 1 - e9877
• Main Authors: Foschetti, D.A., Braga-Neto, M.B., Bolick, D., Moore, J., Alves, LA, Martins, CS, Bomfin, LE, Santos, AAQA, Leitão, RFC, Brito, GAC, Warren, CA
• Format: Journal Article
• Language: English
• Published: Ribeirao Preto Revista Brasileira de Pesquisas Medicas 01-01-2020; Associação Brasileira de Divulgação Científica
• Subjects: A2A adenosine receptor; A2B adenosine receptor; Adenosine; BIOLOGY; Cecum; Clostridium difficile; Clostridium difficile toxins; Epithelial cells; Inflammation; Interleukin 6; Intestine; MEDICINE, RESEARCH & EXPERIMENTAL; Toxin A; A2A adenosine receptor; Adenosine; Clostridium difficile toxins; A2B adenosine receptor; Clostridium difficile
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431x20209877

Clostridium difficile causes intestinal inflammation, which increases adenosine. We compared the expression of adenosine receptors (AR) subtypes A1, A2A, A2B, and A3 in HCT-8, IEC-6 cells, and isolated intestinal epithelial cells, challenged or not with Clostridium difficile toxin A and B (TcdA and TcdB) or infection (CDI). In HCT-8, TcdB induced an early A2BR expression at 6 h and a late A2AR expression at 6 and 24 h. In addition, both TcdA and TcdB increased IL-6 expression at all time-points (peak at 6 h) and PSB603, an A2BR antagonist, decreased IL-6 expression and production. In isolated cecum epithelial cells, TcdA induced an early expression of A2BR at 2s and 6 h, followed by a late expression of A2AR at 6 and 24 h and of A1R at 24 h. In CDI, A2AR and A2BR expressions were increased at day 3, but not at day 7. ARs play a role in regulating inflammation during CDI by inducing an early pro-inflammatory and a late anti-inflammatory response. The timing of interventions with AR antagonist or agonists may be of relevance in treatment of CDI.