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

Abstract

Clostridium difficile causes intestinal inflammation, which increases adenosine. We compared the expression of adenosine receptors (AR) subtypes A 1 , A 2A , A 2B , and A 3 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 A 2B R expression at 6 h and a late A 2A R 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 A 2B R antagonist, decreased IL-6 expression and production. In isolated cecum epithelial cells, TcdA induced an early expression of A 2B R at 2 and 6 h, followed by a late expression of A 2A R at 6 and 24 h and of A 1 R at 24 h. In CDI, A 2A R and A 2B R 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.

How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms?

“…In this regard previous studies have indicated that vitamin D inhibits TNF-α, IFN-γ, IL-1, IL-6, and IL-17, by reducing the p38 MAP kinase activation in human monocytes/macrophages and enhancing the expression level of T-regulatory cells, Th2, M2 macrophages, and IL-10 ( 126 – 131 ). Notably, C. difficile stimulate production of inflammatory cytokines such as IL-8, IL-6, IL-1β, TNF-α, COX-2, and PE2, which are suggested playing crucial roles in CDI pathogenesis as well as SARS-CoV-2 infection ( 132 – 134 ). Given that, vitamin D can help prevent upper respiratory tract infections or reduce the severity of them through increasing the immune modulatory activity by inhibition of transcription level of proinflammatory cytokines such as TNF-α, IFN-γ, IL-17, IL-2, and IL-21 ( 125 , 135 , 136 ).…”

Adenosine A2A receptor and vascular response: role of soluble epoxide hydrolase, adenosine A1 receptor and angiotensin-II

“…This study demonstrated that deletion of A 2A AR (A 2A AR −/− ) is associated with increased in vascular endothelial sEH levels, increased in vascular smooth muscle ω-hydroxylase (CYP4A), increased in A 1 AR and decreased in vascular endothelial CYP-epoxygenase (CYP2C) with changed in NECA and CCPA-dose dependent vascular response compared to C57Bl/6 mice. Adenosine plays an important role in the vascular regulation through activation of four adenosine receptors A 1 AR, A 2A AR, A 2B AR and A 3 AR [2,3,[6][7][8][9][10][11][12][13]. Out of four adenosine receptors A 1 AR and A 3 AR are involve in vasoconstriction [12,16,[43][44][45], whereas A 2A AR and A 2B AR are involve in vascular relaxation [2-4, 18, 46].…”

“…Adenosine is an endogenous nucleoside, which is involved in the modulation of different physiological functions [1][2][3][4], and its effect observed in every tissue and organ system [2][3][4][5]. Adenosine plays an important role in the vascular regulation through activation of four adenosine receptors A 1 AR, A 2A AR, A 2B AR and A 3 AR [2,3,[6][7][8][9][10][11][12][13]. In mouse coronary artery and aorta, vasodilation is caused by A 2A AR and contraction caused by A 1 AR [2-4, 9, 12, 14-16].…”

Mining Anti-Inflammation Molecules From Nippostrongylus brasiliensis-Derived Products Through the Metabolomics Approach

“…Through literature searching, we discovered 14 metabolites with anti-inflammatory or antioxidative properties which could be subclassed into amino acids, benzylisoquinolines, quaternary ammonium salts, pyrimidines, pregnane steroids, purines, biphenyls, and glycerophosphocholines. For example, as a candidate for anti-inflammation, glutamine could crucially influence the long-term treatment outcome of inflammatory (Shimizu and Son, 2007;Araujo et al, 2015); anti-inflammatory (Cruzat et al, 2015;Foschetti et al, 2020;Liu et al, 2020) 10.097 0.002 1.357 0.001 Pyruvate Organic acids and derivatives 87.008 130.075 Anti-inflammatory (Wang et al, 2009;Yang et al, 2016) 1.791 0.049 1.237 0.001 Glutamine Organic acids and derivatives 145.062 374.131 Anti-inflammatory (Ren et al, 2013) 7.87 0.036 2.012 0.009 L-Glutamine Organic acids and derivatives Su 373.919 Anti-inflammatory (Almeida et al, 2020;Paixao et al, 2021) 7.297 0.002 1.028 0.006 Betaine Organic acids and derivatives 118.085 274.605 Neuroprotective (Singhal et al, 2020); antitumor (Kim et al, 2014); antidiabetic (Jiang et al, 2019); anti-inflammatory (Yang et al, 2018) 5 et al, 2021); antitumor (Carroll et al, 2011;Feng et al, 2017); neuroprotective (Vecchi Brumatti et al, 2014;Yu et al, 2018); antiinflammatory (Ammar el et al, 2011;Ma et al, 2017) 15.442 0.011…”