scholarly journals Caffeine Has Different Immunomodulatory Effect on the Cytokine Expression and NLRP3 Inflammasome Function in Various Human Macrophage Subpopulations

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2409
Author(s):  
Elek Gergő Kovács ◽  
Ahmad Alatshan ◽  
Marietta Margit Budai ◽  
Zsolt Czimmerer ◽  
Eduárd Bíró ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Human Monocyte ◽  
Receptor Expression ◽  
Negative Regulator ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Besides its well-known psychoactive effects, caffeine has a broad range of actions. It regulates several physiological mechanisms as well as modulates both native and adaptive immune responses by various ways. Although caffeine is assumed to be a negative regulator of inflammation, the effect on the secretion of pro- and anti-inflammatory cytokines is highly controversial. Macrophages are major mediators of inflammatory responses; however, the various subpopulations develop different effects ranging from the initiation to the resolution of inflammation. Here we report a comparative analysis of the effect of caffeine on two subpopulations of human monocyte-derived macrophages differentiated in the presence of macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), resulting in M-MΦs and GM-MΦs, respectively. We showed that although TNF-α secretion was downregulated in both LPS-activated MΦ subtypes by caffeine, the secretion of IL-8, IL-6, and IL-1β as well as the expression of Nod-like receptors was enhanced in M-MΦs, while it did not change in GM-MΦs. We showed that caffeine (1) altered adenosine receptor expression, (2) changed Akt/AMPK/mTOR signaling pathways, and (3) inhibited STAT1/IL-10 signaling axis in M-MΦs. We hypothesized that these alterations play an important modulatory role in the upregulation of NLRP3 inflammasome-mediated IL-1β secretion in LPS-activated M-MΦs following caffeine treatment.

scholarly journals ATP-Evoked Intracellular Ca2+ Responses in M-CSF Differentiated Human Monocyte-Derived Macrophage are Mediated by P2X4 and P2Y11 Receptor Activation

2019 ◽  
Vol 20 (20) ◽  
pp. 5113 ◽  
Author(s):  
Janice A. Layhadi ◽  
Samuel J. Fountain
Keyword(s):  
Human Monocyte ◽  
Receptor Activation ◽  
Human Macrophage ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Qrt Pcr ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Tissues differentially secrete multiple colony stimulating factors under conditions of homeostasis and inflammation, orientating recruited circulating monocytes to differentiate to macrophage with differing functional phenotypes. Here, we investigated ATP-evoked intracellular Ca2+ responses in human macrophage differentiated with macrophage colony-stimulating factor (M-CSF). Extracellular ATP evoked (EC50 13.3 ± 1.4 μM) robust biphasic intracellular Ca2+ responses that showed a dependency on both metabotropic (P2Y) and ionotropic (P2X) receptors. qRT-PCR and immunocytochemistry revealed the expression of P2Y1, P2Y2, P2Y6, P2Y11, P2Y13, P2X1, P2X4, P2X5, and P2X7. Pharmacological analysis revealed contribution of only P2X4 and P2Y11 to the Ca2+ response evoked by maximal ATP concentrations (100 µM). This study reveals the contribution of P2X4 and P2Y11 receptor activation to ATP-evoked intracellular Ca2+ responses, and makes comparison with macrophage differentiated using granulocyte colony-stimulating factor (GM-CSF).

In vivo effects of macrophage colony-stimulating factor on human monocyte function

1991 ◽  
Vol 77 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Asim Khwaja ◽  
Beryl Johnson ◽  
Ian E. Addison ◽  
Kwee Yong ◽  
Karen Ruthven ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Colony Stimulating Factor ◽  
Monocyte Function ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
In Vivo Effects ◽  
Stimulating Factor

scholarly journals Paradoxical role of alveolar macrophage-derived granulocyte-macrophage colony-stimulating factor in pulmonary host defense post-bone marrow transplantation

2008 ◽  
Vol 295 (1) ◽  
pp. L114-L122 ◽  
Author(s):  
Megan N. Ballinger ◽  
Leah L. N. Hubbard ◽  
Tracy R. McMillan ◽  
Galen B. Toews ◽  
Marc Peters-Golden ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Host Defense ◽  
Receptor Expression ◽  
Colony Stimulating Factor ◽  
Wild Type ◽  
Bacterial Killing ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Impaired host defense post-bone marrow transplant (BMT) is related to overproduction of prostaglandin E2(PGE2) by alveolar macrophages (AMs). We show AMs post-BMT overproduce granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas GM-CSF in lung homogenates is impaired both at baseline and in response to infection post-BMT. Homeostatic regulation of GM-CSF may occur by hematopoietic/structural cell cross talk. To determine whether AM overproduction of GM-CSF influenced immunosuppression post-BMT, we compared mice that received BMT from wild-type donors (control BMT) or mice that received BMT from GM-CSF−/− donors (GM-CSF−/− BMT) with untransplanted mice. GM-CSF−/− BMT mice were less susceptible to pneumonia with Pseudomonas aeruginosa compared with control BMT mice and showed antibacterial responses equal to or better than untransplanted mice. GM-CSF−/− BMT AMs displayed normal phagocytosis and a trend toward enhanced bacterial killing. Surprisingly, AMs from GM-CSF−/− BMT mice overproduced PGE2, but expression of the inhibitory EP2receptor was diminished. As a consequence of decreased EP2receptor expression, we found diminished accumulation of cAMP in response to PGE2stimulation in GM-CSF−/− BMT AMs compared with control BMT AMs. In addition, GM-CSF−/− BMT AMs retained cysteinyl leukotriene production and normal TNF-α response compared with AMs from control BMT mice. GM-CSF−/− BMT neutrophils also showed improved bacterial killing. Although genetic ablation of GM-CSF in hematopoietic cells post-BMT improved host defense, transplantation of wild-type bone marrow into GM-CSF−/− recipients demonstrated that parenchymal cell-derived GM-CSF is necessary for effective innate immune responses post-BMT. These results highlight the complex regulation of GM-CSF and innate immunity post-BMT.

Human macrophage colony-stimulating factor levels in cerebrospinal fluid

Cytokine ◽  
1993 ◽  
Vol 5 (3) ◽  
pp. 250-254 ◽  
Author(s):  
Kazuya Shimoda ◽  
Seiichi Okamura ◽  
Yumi Mizuno ◽  
Naoki Harada ◽  
Akira Kubota ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor
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