Abstract
It has been shown that mesenchymal stem cells (MSCs) express all four adenosine receptors' subtypes, and stimulation of these receptors plays an active role in bone marrow-derived mesenchymal stem cell proliferation and differentiation. The interaction between MSCs and immunocytes, such as neutrophils, has been investigated in some recent studies. This study was carried out to investigate the effects of caffeine as an adenosine antagonist on the effects of bone marrow-derived MSCs on neutrophils. Mesenchymal stem cells were isolated from the bone marrow of rats and pulsed with different concentrations of caffeine (0.1, 0.5 and 1 mM) at different times (24, 48 and 72 h). Mesenchymal stem cells were co-cultured with neutrophils for 4 h and the functions of neutrophils were evaluated. The findings showed that MSCs pulsed with caffeine at low to moderate concentrations preserved the neutral red uptake by neutrophils and established the MSCs' ability to protect neutrophils from apoptosis. Mesenchymal stem cells treated with caffeine increased the phagocytosis of neutrophils and simultaneously diminished the production of potentially harmful reactive oxygen substances, more profound than MSCs without treatment. Nevertheless, a high concentration of caffeine could interfere with some aspects of the crosstalk between MSCs and neutrophils. These findings may offer new insight into the potential mechanisms underlying the immunomodulatory effects of caffeine.
Highlights
Caffeine (1, 3, 7-trimethylxanthine) is a natural product and a member of the methylxanthine family of drugs, which can be found in coffee, tea, soft drinks, chocolate, kola nuts, and certain medicines.[1,2] Caffeine possesses various effects on different body systems, including endocrine, cardiovascular, respiratory, urinary, gastrointestinal metabolism, immunity, and especially the central nervous system.[3,4] caffeine is the world’s most widely and legally consumed psychoactive drug.[3]
The findings showed that mesenchymal stem cells (MSCs) pulsed with caffeine at low to moderate concentrations preserved the neutral red uptake by neutrophils and established the MSCs’ ability to protect neutrophils from apoptosis
MSCs pulsed with 0.5 mM of caffeine for 72 h and MSCs treated with 1 mM of caffeine for 24, 48 and 72 h significantly diminished the survivability of neutrophils, compared to the control group (Fig. 1)
Summary
Caffeine (1, 3, 7-trimethylxanthine) is a natural product and a member of the methylxanthine family of drugs, which can be found in coffee, tea, soft drinks, chocolate, kola nuts, and certain medicines.[1,2] Caffeine possesses various effects on different body systems, including endocrine, cardiovascular, respiratory, urinary, gastrointestinal metabolism, immunity, and especially the central nervous system.[3,4] caffeine is the world’s most widely and legally consumed psychoactive drug.[3] Caffeine is structurally similar to adenosine. It has been shown that mesenchymal stem cells (MSCs) express all four adenosine receptors’ subtypes, and stimulation of these receptors plays an active role in bone marrow-derived mesenchymal stem cell proliferation and differentiation. The interaction between MSCs and immunocytes, such as neutrophils, has been investigated in some recent studies
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